start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=3 article-no= start-page=e15040 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240301 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Elevated expression of interleukin-6 (IL-6) and serum amyloid A (SAA) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of IL-6 through Toll-like receptor ligands and SAA en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL-6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL-6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL-6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll-like receptor (TLR) ligands, pathogen-associated and damage-associated molecular pattern molecules. In vitro, TLR ligands induced IL-6 expression via NF-κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL-6 via TLR1/2 and NF-κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR-mediated persistent skin inflammation might increase the risk of IL-6-related systemic complications, including RDEB. en-copyright= kn-copyright= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajitaAi en-aut-sei=Kajita en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasuiKen‐Ichi en-aut-sei=Hasui en-aut-mei=Ken‐Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsudaYoshihiro en-aut-sei=Matsuda en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=epidermolysis bullosa kn-keyword=epidermolysis bullosa en-keyword=fibroblasts kn-keyword=fibroblasts en-keyword=IL-6 kn-keyword=IL-6 en-keyword=keratinocytes kn-keyword=keratinocytes en-keyword=serum amyloid A kn-keyword=serum amyloid A END start-ver=1.4 cd-journal=joma no-vol=14 cd-vols= no-issue= article-no= start-page=1239598 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=“Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases en-subtitle= kn-subtitle= en-abstract= kn-abstract=Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MukaiTomoyuki en-aut-sei=Mukai en-aut-mei=Tomoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawakamiYoshio en-aut-sei=Kawakami en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Immunology and Molecular Genetics, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=epidermal keratinocytes kn-keyword=epidermal keratinocytes en-keyword=input cytokines kn-keyword=input cytokines en-keyword=output cytokines kn-keyword=output cytokines en-keyword=biologics kn-keyword=biologics en-keyword=inflammatory skin diseases kn-keyword=inflammatory skin diseases END start-ver=1.4 cd-journal=joma no-vol=135 cd-vols= no-issue=2 article-no= start-page=78 end-page=80 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20230801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Epidermolysis bullosa (EB) kn-title=表皮水疱症 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MiyakeTomoko en-aut-sei=Miyake en-aut-mei=Tomoko kn-aut-name=三宅智子 kn-aut-sei=三宅 kn-aut-mei=智子 aut-affil-num=1 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name=森実真 kn-aut-sei=森実 kn-aut-mei=真 aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Hospital kn-affil=岡山大学病院　皮膚科 affil-num=2 en-affil=Department of Dermatology, Okayama University Hospital kn-affil=岡山大学病院　皮膚科 en-keyword=表皮水疱症状 kn-keyword=表皮水疱症状 en-keyword=コラーゲンZ kn-keyword=コラーゲンZ en-keyword=ケラチン kn-keyword=ケラチン END start-ver=1.4 cd-journal=joma no-vol=107 cd-vols= no-issue=1 article-no= start-page=2 end-page=7 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=202207 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Aberrant serine protease activities in atopic dermatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Atopic dermatitis (AD) is a chronic inflammatory skin disease; the three major factors responsible for AD, i.e., epidermal barrier dysfunction, allergic inflammation, and itching, interact with each other to form a pathological condition. Excessive protease activities are characteristic abnormalities that affect the epi-dermal barrier in patients with AD. In normal skin, epidermal serine protease activities are controlled by kallikrein-related peptidases (KLKs) and their inhibitors, including lympho-epithelial Kazal-type-related inhibitor (LEKTI). In AD lesions, KLKs are excessively expressed, which results in the enhancement of epi-dermal serine protease activities and facilitates the invasion by allergens and microorganisms. In addition, some KLKs can activate protease-activated receptor 2 (PAR2) in epidermal keratinocytes and peripheral nerves, resulting in the induction of inflammation and itching. Furthermore, in AD patients with single nucleotide polymorphism (SNP) such as E420K and D386N of SPINK5 which encodes LEKTI, LEKTI function is attenuated, resulting in the activation of KLKs and easy invasion by allergens and microorganisms. Further analysis is needed to elucidate the detailed mechanism underlying the control of serine protease activities, which may lead to the development of new therapeutic and prophylactic agents for AD.(c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved. en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Atopic dermatitis kn-keyword=Atopic dermatitis en-keyword=Serine protease kn-keyword=Serine protease en-keyword=Kallikrein-related peptidases kn-keyword=Kallikrein-related peptidases en-keyword=Lympho-epithelial Kazal-type-related kn-keyword=Lympho-epithelial Kazal-type-related en-keyword=inhibitor kn-keyword=inhibitor en-keyword=Protease -activated receptor 2 kn-keyword=Protease -activated receptor 2 END start-ver=1.4 cd-journal=joma no-vol=22 cd-vols= no-issue=23 article-no= start-page=12659 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20211123 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifaceted Analysis of IL-23A-and/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-alpha, IL-17A, and interferon (IFN)-gamma, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer. en-copyright= kn-copyright= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TangNina en-aut-sei=Tang en-aut-mei=Nina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UrakamiHitoshi en-aut-sei=Urakami en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajitaAi en-aut-sei=Kajita en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SasakuraMinori en-aut-sei=Sasakura en-aut-mei=Minori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=JiangFan en-aut-sei=Jiang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TomonobuNahoko en-aut-sei=Tomonobu en-aut-mei=Nahoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=SakaguchiMasakiyo en-aut-sei=Sakaguchi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OuchidaMamoru en-aut-sei=Ouchida en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=12 en-affil=Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=13 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= en-keyword=psoriasis vulgaris kn-keyword=psoriasis vulgaris en-keyword=interleukin (IL) 23 kn-keyword=interleukin (IL) 23 en-keyword=IL-39 kn-keyword=IL-39 en-keyword=p19 kn-keyword=p19 en-keyword=Epstein-Barr virus-induced (EBI) 3 kn-keyword=Epstein-Barr virus-induced (EBI) 3 en-keyword=tildrakizumab kn-keyword=tildrakizumab END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=3 article-no= start-page=913 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200130 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis en-subtitle= kn-subtitle= en-abstract= kn-abstract=The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC's serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD. en-copyright= kn-copyright= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuganumaMutsumi en-aut-sei=Suganuma en-aut-mei=Mutsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakeichiTakuya en-aut-sei=Takeichi en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KonoMichihiro en-aut-sei=Kono en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IsokaneYuki en-aut-sei=Isokane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SunagawaKo en-aut-sei=Sunagawa en-aut-mei=Ko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KajitaAi en-aut-sei=Kajita en-aut-mei=Ai kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MiyakeTomoko en-aut-sei=Miyake en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HiraiYoji en-aut-sei=Hirai en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AkiyamaMasashi en-aut-sei=Akiyama en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Dermatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Dermatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Dermatology and Plastic Surgery, Akita University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=10 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=11 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=12 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=13 en-affil=Department of Dermatology, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= en-keyword=atopic dermatitis kn-keyword=atopic dermatitis en-keyword=serine proteases kn-keyword=serine proteases en-keyword=kallikrein-related peptidases kn-keyword=kallikrein-related peptidases en-keyword=epidermal barrier dysfunction kn-keyword=epidermal barrier dysfunction en-keyword=lympho-epithelial Kazal-type-related inhibitor (LEKTI) kn-keyword=lympho-epithelial Kazal-type-related inhibitor (LEKTI) en-keyword=SPINK5 kn-keyword=SPINK5 en-keyword=filaggrin kn-keyword=filaggrin END start-ver=1.4 cd-journal=joma no-vol=92 cd-vols= no-issue=12 article-no= start-page=3689 end-page=3696 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The aim of the measurement of Epstein‐Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epstein‐Barr virus (EBV) DNA load in the blood increases in posttransplant lymphoproliferative disorders and chronic active EBV infection. In this report, we analyzed the EBV DNA load in the peripheral blood mononuclear cells (PBMCs) and plasma of patients with hydroa vacciniforme (HV) and/or hypersensitivity to mosquito bites (HMB) to understand the clinical significance of EBV DNA load. All 30 patients showed high DNA loads in the PBMCs over the cut‐off level. Of 16 plasma samples, extremely high in two samples obtained from patients with hemophagocytic lymphohistiocytosis (HLH). The amount of cell‐free DNA in plasma was correlated to the serum levels of lactate dehydrogenase and inversely correlated to platelet counts. These results indicate that the EBV DNA load in PBMCs can provide one of the diagnostic indicators for HV and HMB and marked elevation of cell‐free EBV DNA in plasma might be related to cytolysis such as that observed in HLH. en-copyright= kn-copyright= en-aut-name=MiyakeTomoko en-aut-sei=Miyake en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HiraiYoji en-aut-sei=Hirai en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoTakenobu en-aut-sei=Yamamoto en-aut-mei=Takenobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HamadaToshihisa en-aut-sei=Hamada en-aut-mei=Toshihisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Fujii Kazuyasu en-aut-sei=Fujii en-aut-mei= Kazuyasu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=mamuraHideaki en-aut-sei=mamura en-aut-mei=Hideaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Pediatrics, Faculty of Medicine, University of Miyazaki kn-affil= affil-num=8 en-affil=Department of Dermatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Epstein-Barr Virus DNA load kn-keyword=Epstein-Barr Virus DNA load en-keyword=hydroa vaccniforme kn-keyword=hydroa vaccniforme en-keyword=hypersensitivity to mosquito bite kn-keyword=hypersensitivity to mosquito bite en-keyword=hemophagocytic lymphohistiocytosis kn-keyword=hemophagocytic lymphohistiocytosis END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=1 article-no= start-page=40 end-page=46 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180516 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Toll‐like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND:
Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date.
AIM:
To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts.
METHODS:
We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied.
RESULTS:
SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs.
CONCLUSIONS:
Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa. en-copyright= kn-copyright= en-aut-name=MorizaneS. en-aut-sei=Morizane en-aut-mei=S. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajitaA. en-aut-sei=Kajita en-aut-mei=A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MizunoK. en-aut-sei=Mizuno en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Takiguchi T. en-aut-sei=Takiguchi en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IwatsukiK. en-aut-sei=Iwatsuki en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=96 cd-vols= no-issue=1 article-no= start-page=26 end-page=32 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190821 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TNF-α and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND:
Serine proteases have important roles in skin barrier function and desquamation, and the aberrant expression or the dysfunction of serine proteases is associated with the pathogenesis of skin diseases. Serine protease activities are tightly regulated by serine proteases such as kallikrein-related peptidases (KLKs) and serine protease inhibitors such as lympho-epithelial Kazal-type related inhibitor (LEKTI). For a better understating of diseases' pathogenesis, the regulation mechanism of serine proteases and the inhibitors' expression in epidermal keratinocytes must be clarified.
OBJECTIVES:
To investigate the effects of the cytokines on the expression of LEKTI in epidermal keratinocytes.
METHODS:
Normal human epidermal keratinocytes (NHEKs) were stimulated with panels of inflammatory cytokines. The expression of serine protease inhibitors was analyzed using quantitative real-time PCR and ELISA. LEKTI expression in normal human skin and lesions from psoriasis or atopic dermatitis (AD) were analyzed by immunohistochemically and tape-stripping. Trypsin- and chymotrypsin-like serine protease activities in culture supernatants were measured by using specific substrates.
RESULTS:
TNF-α and IL-17A significantly induced the expression of LEKTI in NHEKs. The immunohistochemical and tape-stripping analysis revealed that psoriatic skin lesions had higher LEKTI expression compared to normal skin and AD lesions. Trypsin- and chymotrypsin-like protease activities in the culture media were upregulated 3-5 days later but attenuated 6-7 days later period by these cytokines.
CONCLUSIONS:
In epidermal keratinocytes, the Th1&Th17 cytokines TNF-α and IL-17A induce the expression of serine protease inhibitor LEKTI, and it might occur to suppress the increase in the serine protease activities under inflammation. en-copyright= kn-copyright= en-aut-name=SugiharaSatoru en-aut-sei=Sugihara en-aut-mei=Satoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugimotoSaeko en-aut-sei=Sugimoto en-aut-mei=Saeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TachibanaKota en-aut-sei=Tachibana en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobashiMina en-aut-sei=Kobashi en-aut-mei=Mina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomuraHayato en-aut-sei=Nomura en-aut-mei=Hayato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MiyakeTomoko en-aut-sei=Miyake en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HiraiYoji en-aut-sei=Hirai en-aut-mei=Yoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamasakiOsamu en-aut-sei=Yamasaki en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Departments of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Epidermal keratinocyte kn-keyword=Epidermal keratinocyte en-keyword=IL-17A kn-keyword=IL-17A en-keyword=Lympho-epithelial Kazal-type inhibitor kn-keyword=Lympho-epithelial Kazal-type inhibitor en-keyword=Serine protease inhibitor kn-keyword=Serine protease inhibitor en-keyword=TNF-α kn-keyword=TNF-α END start-ver=1.4 cd-journal=joma no-vol=171 cd-vols= no-issue=3 article-no= start-page=492 end-page=498 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201409 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Cathelicidin antimicrobial peptide LL-37 augments interferon-beta expression and antiviral activity induced by double-stranded RNA in keratinocytes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Cathelicidin antimicrobial peptide LL-37 has the capacity to kill a wide range of microbes and to modify host immunity. Recently, our group observed that the activation of keratinocytes by LL-37 and DNA greatly increases interferon (IFN)-beta through Toll-like receptor (TLR) 9. However, the effect of LL-37 on the induction of IFN-beta through TLR3, a sensor of double-stranded (ds) RNA, in keratinocytes is not well known. Objectives To investigate whether LL-37 could affect TLR3 signalling and antiviral activity in normal human epidermal keratinocytes (NHEKs). Methods We investigated the production of IFN-beta in NHEKs stimulated with a TLR3 ligand, poly (I:C), in the presence of LL-37. To examine the effect of LL-37 and poly (I:C) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type-1 was carried out. The uptake of poly (I:C) conjugated with fluorescein isothiocyanate (FITC) into the keratinocytes was observed in the presence of LL-37. Immunostaining for TLR3 and LL-37 was performed using skin samples from HS. Results LL-37 and poly (I:C) synergistically induced the expression of IFN-beta in NHEKs. Furthermore, co-stimulation with LL-37 and poly (I:C) significantly decreased the viral plaque numbers compared with poly (I:C) or LL-37 alone. LL-37 enhanced the uptake of FITC-conjugated poly (I:C) into cells. Immunohistochemical analysis demonstrated that the expression of TLR3 and LL-37 is up-regulated in HS lesions. Conclusions Our findings suggest that LL-37 augments the antiviral activity induced by dsRNA in keratinocytes, which may contribute to the innate immune response to cutaneous viral infections such as HS. en-copyright= kn-copyright= en-aut-name=TakiguchiT en-aut-sei=Takiguchi en-aut-mei=T kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MorizaneS en-aut-sei=Morizane en-aut-mei=S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamamotoT en-aut-sei=Yamamoto en-aut-mei=T kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KajitaA en-aut-sei=Kajita en-aut-mei=A kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IkedaK en-aut-sei=Ikeda en-aut-mei=K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwatsukiK en-aut-sei=Iwatsuki en-aut-mei=K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Kawasaki Med Univ, Dept Dermatol affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=3 article-no= start-page=217 end-page=220 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20131202 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Th2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis kn-title=Th２サイトカインはアトピー性皮膚炎患者における カリクレイン７の発現と機能を増強する en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name=森実真 kn-aut-sei=森実 kn-aut-mei=真 aut-affil-num=1 ORCID= en-aut-name=YamasakiKenshi en-aut-sei=Yamasaki en-aut-mei=Kenshi kn-aut-name=山崎研志 kn-aut-sei=山崎 kn-aut-mei=研志 aut-affil-num=2 ORCID= en-aut-name=KajitaAi en-aut-sei=Kajita en-aut-mei=Ai kn-aut-name=梶田藍 kn-aut-sei=梶田 kn-aut-mei=藍 aut-affil-num=3 ORCID= en-aut-name=IkedaKazuko en-aut-sei=Ikeda en-aut-mei=Kazuko kn-aut-name=池田佳寿子 kn-aut-sei=池田 kn-aut-mei=佳寿子 aut-affil-num=4 ORCID= en-aut-name=ZhanMaosheng en-aut-sei=Zhan en-aut-mei=Maosheng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AoyamaYumi en-aut-sei=Aoyama en-aut-mei=Yumi kn-aut-name=青山裕美 kn-aut-sei=青山 kn-aut-mei=裕美 aut-affil-num=6 ORCID= en-aut-name=Richard L Gallo en-aut-sei=Richard L Gallo en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwatsukiKeiji en-aut-sei=Iwatsuki en-aut-mei=Keiji kn-aut-name=岩月啓氏 kn-aut-sei=岩月 kn-aut-mei=啓氏 aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　皮膚科学 affil-num=2 en-affil= kn-affil=東北大学大学院医学系研究科　皮膚科学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　皮膚科学 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　皮膚科学 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　皮膚科学 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　皮膚科学 affil-num=7 en-affil= kn-affil=米国カリフォルニア大学サンディエゴ校医学部　皮膚科学 affil-num=8 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　皮膚科学 en-keyword=アトピー性皮膚炎 kn-keyword=アトピー性皮膚炎 en-keyword=Th２サイトカイン kn-keyword=Th２サイトカイン en-keyword=カリクレイン kn-keyword=カリクレイン en-keyword=表皮角化細胞 kn-keyword=表皮角化細胞 END start-ver=1.4 cd-journal=joma no-vol=167 cd-vols= no-issue=2 article-no= start-page=252 end-page=261 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Detection of antibodies against the non-calcium-dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Antidesmoglein (anti-Dsg) 3 serum antibody titres are usually correlated with the disease activity of pemphigus vulgaris (PV), but some patients retain high titres even in remission. Objectives The aim of our study was to determine whether anti-Dsg3 antibodies in PV sera recognized calcium (Ca2+)-dependent or non-Ca2+-dependent epitopes, and to evaluate their pathogenicity. Methods Dsg3 baculoprotein-coated enzyme-linked immunosorbent assay (ELISA) plates were treated with 0.5 mmol L-1 ethylenediaminetetraacetic acid (EDTA). The binding ability of anti-Dsg3 monoclonal antibodies (mAbs) was analysed. Eight of the 83 patients with PV who were screened had elevated Dsg3 ELISA index values > 100 in remission. The binding ability of these PV sera was analysed. We evaluated the pathogenicity of anti-Dsg3 serum antibodies against the non-Ca2+-dependent epitopes using a dissociation assay. Results The reactivity of pathogenic anti-Dsg3 mAbs against the Ca2+-dependent epitopes diminished markedly in the EDTA-treated ELISA, whereas no such reduction was observed in mAbs against the non-Ca2+-dependent epitopes. The sera of all the patients contained antibodies against both Ca2+-dependent and non-Ca2+-dependent epitopes. In six out of the eight patients, the ratio of antibodies against Ca2+-dependent to non-Ca2+-dependent epitopes decreased in remission. EDTA-treated Dsg3 baculoproteins adsorbed anti-Dsg3 serum antibodies against the non-Ca2+-dependent epitopes, but the remnant PV antibodies retained the ability to induce acantholysis in the dissociation assay. Conclusions We have established an assay to measure indirectly the titres of anti-Dsg3 serum antibodies against the Ca2+-dependent epitopes, based on the differences between EDTA-untreated and EDTA-treated ELISA index values, as a routine laboratory test to reflect the pathogenic anti-Dsg3 serum antibody titres more accurately. en-copyright= kn-copyright= en-aut-name=KamiyaK en-aut-sei=Kamiya en-aut-mei=K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AoyamaY en-aut-sei=Aoyama en-aut-mei=Y kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShirafujiY en-aut-sei=Shirafuji en-aut-mei=Y kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HamadaT en-aut-sei=Hamada en-aut-mei=T kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorizaneS en-aut-sei=Morizane en-aut-mei=S kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=FujiiK en-aut-sei=Fujii en-aut-mei=K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisataK en-aut-sei=Hisata en-aut-mei=K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwatsukiK en-aut-sei=Iwatsuki en-aut-mei=K kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=20061231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=ウイルス性水疱の形成におけるCD4陽性細胞傷害性T細胞とCD8陽性細胞傷害性T細胞の役割 kn-title=The role of CD4 and CD8 cytotoxic T lymphocytes in the formation of viral vesicles en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MorizaneShin en-aut-sei=Morizane en-aut-mei=Shin kn-aut-name=森実真 kn-aut-sei=森実 kn-aut-mei=真 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END