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=20060324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=軽中等度高血圧患者における早朝家庭血圧と脈波伝播速度に対するテルミサルタンの臨床効果 kn-title=Practical Efficacy of Telmisartan for Decreasing Morning Home Blood Pressure and Pulse Wave Velocity in Patients with Mild-to-Moderate Hypertension en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UchidaHaruhito en-aut-sei=Uchida en-aut-mei=Haruhito kn-aut-name=内田治仁 kn-aut-sei=内田 kn-aut-mei=治仁 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=2 article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130219 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Decreased Level of Serum Soluble Klotho Is an Independent Biomarker Associated with Arterial Stiffness in Patients with Chronic Kidney Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD). Methods: We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification. Results: The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV >= 1400 cm/sec, atherosclerosis defined as maximum IMT >= 1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075). Conclusions: Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted. en-copyright= kn-copyright= en-aut-name=KitagawaMasashi en-aut-sei=Kitagawa en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorinagaHiroshi en-aut-sei=Morinaga en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueTatsuyuki en-aut-sei=Inoue en-aut-mei=Tatsuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakiueKeiichi en-aut-sei=Takiue en-aut-mei=Keiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OgawaAyu en-aut-sei=Ogawa en-aut-mei=Ayu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamanariToshio en-aut-sei=Yamanari en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KikumotoYoko en-aut-sei=Kikumoto en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaHaruhito Adam en-aut-sei=Uchida en-aut-mei=Haruhito Adam kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MaeshimaYohei en-aut-sei=Maeshima en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NakamuraKazufumi en-aut-sei=Nakamura en-aut-mei=Kazufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=ItoHiroshi en-aut-sei=Ito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=11 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=12 en-affil= kn-affil=Okayama Univ, Dept Cardiovasc Med, Grad Sch Med Dent & Pharmaceut Sci affil-num=13 en-affil= kn-affil=Okayama Univ, Dept Cardiovasc Med, Grad Sch Med Dent & Pharmaceut Sci affil-num=14 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci END start-ver=1.4 cd-journal=joma no-vol=8 cd-vols= no-issue=8 article-no= start-page=e72214 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130819 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Calpain-2 Compensation Promotes Angiotensin II-Induced Ascending and Abdominal Aortic Aneurysms in Calpain-1 Deficient Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Objective Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, we examined the relative contribution of calpain isoforms in AngII-induced ascending and abdominal AA development. Methodology/Results To investigate the relative contribution of calpain-1 and -2 in development of AngII-induced AAs, male LDLr −/− mice that were either calpain-1 +/+ or −/− were fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min) for 4 weeks. Calpain-1 deficiency had no significant effect on body weight or blood pressure during AngII infusion. Moreover, calpain-1 deficiency showed no discernible effects on AngII-induced ascending and abdominal AAs. Interestingly, AngII infusion induced increased expression of calpain-2 protein, thus compensating for total calpain activity in aortas of calpain-1 deficient mice. Oral administration of BDA-410, a calpain inhibitor, along with AngII-infusion significantly attenuated AngII-induced ascending and abdominal AA formation in both calpain-1 +/+ and −/− mice as compared to vehicle administered mice. Furthermore, BDA-410 administration attenuated AngII-induced aortic medial hypertrophy and macrophage accumulation. Western blot and immunostaining analyses revealed BDA-410 administration attenuated AngII-induced C-terminal fragmentation of filamin A, an actin binding cytoskeletal protein in aorta. Conclusion Calpain-2 compensates for loss of calpain-1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation in mice. en-copyright= kn-copyright= en-aut-name=SubramanianVenkateswaran en-aut-sei=Subramanian en-aut-mei=Venkateswaran kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MoorleghenJessica J. en-aut-sei=Moorleghen en-aut-mei=Jessica J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=BalakrishnanAnju en-aut-sei=Balakrishnan en-aut-mei=Anju kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HowattDeborah A. en-aut-sei=Howatt en-aut-mei=Deborah A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ChishtiAthar H. en-aut-sei=Chishti en-aut-mei=Athar H. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=2 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=3 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=4 en-affil= kn-affil=Saha Cardiovascular Research Center, University of Kentucky affil-num=5 en-affil= kn-affil=Department of Molecular Physiology and Pharmacology, Sackler School Programs in Physiology, Pharmacology, and Microbiology, Tufts University School of Medicine affil-num=6 en-affil= kn-affil=Department of Medicine and Clinical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences END start-ver=1.4 cd-journal=joma no-vol=126 cd-vols= no-issue=1 article-no= start-page=1 end-page=6 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophages kn-title=糖尿病の腎臓においてcholecystokininはマクロファージに対する抗炎症作用を介した新規の保護効果を発揮する en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MiyamotoSatoshi en-aut-sei=Miyamoto en-aut-mei=Satoshi kn-aut-name=宮本聡 kn-aut-sei=宮本 kn-aut-mei=聡 aut-affil-num=1 ORCID= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name=四方賢一 kn-aut-sei=四方 kn-aut-mei=賢一 aut-affil-num=2 ORCID= en-aut-name=MiyasakaKyoko en-aut-sei=Miyasaka en-aut-mei=Kyoko kn-aut-name=宮坂京子 kn-aut-sei=宮坂 kn-aut-mei=京子 aut-affil-num=3 ORCID= en-aut-name=OkadaShinichi en-aut-sei=Okada en-aut-mei=Shinichi kn-aut-name=岡田震一 kn-aut-sei=岡田 kn-aut-mei=震一 aut-affil-num=4 ORCID= en-aut-name=SasakiMotofumi en-aut-sei=Sasaki en-aut-mei=Motofumi kn-aut-name=佐々木基史 kn-aut-sei=佐々木 kn-aut-mei=基史 aut-affil-num=5 ORCID= en-aut-name=KoderaRyo en-aut-sei=Kodera en-aut-mei=Ryo kn-aut-name=小寺亮 kn-aut-sei=小寺 kn-aut-mei=亮 aut-affil-num=6 ORCID= en-aut-name=HirotaDaisho en-aut-sei=Hirota en-aut-mei=Daisho kn-aut-name=廣田大昌 kn-aut-sei=廣田 kn-aut-mei=大昌 aut-affil-num=7 ORCID= en-aut-name=KajitaniNobuo en-aut-sei=Kajitani en-aut-mei=Nobuo kn-aut-name=梶谷展生 kn-aut-sei=梶谷 kn-aut-mei=展生 aut-affil-num=8 ORCID= en-aut-name=TakatsukaTetsuharu en-aut-sei=Takatsuka en-aut-mei=Tetsuharu kn-aut-name=高塚哲全 kn-aut-sei=高塚 kn-aut-mei=哲全 aut-affil-num=9 ORCID= en-aut-name=Kataoka UsuiHitomi en-aut-sei=Kataoka Usui en-aut-mei=Hitomi kn-aut-name=片岡仁美 kn-aut-sei=片岡 kn-aut-mei=仁美 aut-affil-num=10 ORCID= en-aut-name=NishishitaShingo en-aut-sei=Nishishita en-aut-mei=Shingo kn-aut-name=西下伸吾 kn-aut-sei=西下 kn-aut-mei=伸吾 aut-affil-num=11 ORCID= en-aut-name=Horiguchi SatoChikage en-aut-sei=Horiguchi Sato en-aut-mei=Chikage kn-aut-name=堀口千景 kn-aut-sei=堀口 kn-aut-mei=千景 aut-affil-num=12 ORCID= en-aut-name=FunakoshiAkihiro en-aut-sei=Funakoshi en-aut-mei=Akihiro kn-aut-name=船越顕博 kn-aut-sei=船越 kn-aut-mei=顕博 aut-affil-num=13 ORCID= en-aut-name=NishimoriHisakazu en-aut-sei=Nishimori en-aut-mei=Hisakazu kn-aut-name=西森久和 kn-aut-sei=西森 kn-aut-mei=久和 aut-affil-num=14 ORCID= en-aut-name=UchidaHaruhito Adam en-aut-sei=Uchida en-aut-mei=Haruhito Adam kn-aut-name=内田治仁 kn-aut-sei=内田 kn-aut-mei=治仁 aut-affil-num=15 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name=小川大輔 kn-aut-sei=小川 kn-aut-mei=大輔 aut-affil-num=16 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name=槇野博史 kn-aut-sei=槇野 kn-aut-mei=博史 aut-affil-num=17 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=3 en-affil= kn-affil=東京家政大学 栄養学科 affil-num=4 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=8 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=9 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=10 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=11 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=12 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=13 en-affil= kn-affil=国立病院機構九州がんセンター 消化器肝胆膵内科 affil-num=14 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 血液・腫瘍・呼吸器内科学 affil-num=15 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=16 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 affil-num=17 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 腎・免疫・内分泌代謝内科学 en-keyword=cholecystokinin kn-keyword=cholecystokinin en-keyword=糖尿病性腎症 kn-keyword=糖尿病性腎症 en-keyword=抗炎症作用 kn-keyword=抗炎症作用 en-keyword=腎保護効果 kn-keyword=腎保護効果 END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=9 article-no= start-page=1576 end-page=1580 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200618 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Tubulointerstitial Nephritis Cases With IgM-Positive Plasma Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=Matsuoka-UchiyamaNatsumi en-aut-sei=Matsuoka-Uchiyama en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TsujiKenji en-aut-sei=Tsuji en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FukushimaKazuhiko en-aut-sei=Fukushima en-aut-mei=Kazuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KitamuraShinji en-aut-sei=Kitamura en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SugiyamaHitoshi en-aut-sei=Sugiyama en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiNaoki en-aut-sei=Takahashi en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwanoMasayuki en-aut-sei=Iwano en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Nephrology, Faculty of Medical Science, University of Fukui kn-affil= affil-num=8 en-affil=Department of Nephrology, Faculty of Medical Science, University of Fukui kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= END start-ver=1.4 cd-journal=joma no-vol=132 cd-vols= no-issue=2 article-no= start-page=108 end-page=109 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200803 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Community-based medical collaboration kn-title=地域医療連携 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name=内田治仁 kn-aut-sei=内田 kn-aut-mei=治仁 aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil=岡山大学大学院医歯薬学総合研究科 CKD・CVD 地域連携包括医療学 END start-ver=1.4 cd-journal=joma no-vol=134 cd-vols= no-issue=20 article-no= start-page=2771 end-page=2787 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201030 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=The aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight percent of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis. en-copyright= kn-copyright= en-aut-name=HadaYoshiko en-aut-sei=Hada en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito A. en-aut-sei=Uchida en-aut-mei=Haruhito A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 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=3 ORCID= en-aut-name=KojimaFumiaki en-aut-sei=Kojima en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshidaMasashi en-aut-sei=Yoshida en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakeuchiHidemi en-aut-sei=Takeuchi en-aut-mei=Hidemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KakioYuki en-aut-sei=Kakio en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OtakaNozomu en-aut-sei=Otaka en-aut-mei=Nozomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MoritaYoshitaka en-aut-sei=Morita en-aut-mei=Yoshitaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Rheumatology, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Pharmacology, Kitasato University School of Allied Health Sciences kn-affil= affil-num=5 en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= affil-num=9 en-affil=Department of Rheumatology, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science kn-affil= en-keyword= MR16-1 kn-keyword= MR16-1 en-keyword=interleukin-1 receptor antagonist kn-keyword=interleukin-1 receptor antagonist en-keyword=aortitis kn-keyword=aortitis en-keyword=arthritis kn-keyword=arthritis en-keyword=LV hypertrophy kn-keyword=LV hypertrophy END start-ver=1.4 cd-journal=joma no-vol=2021 cd-vols= no-issue= article-no= start-page=1 end-page=8 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210413 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Macrophage en-subtitle= kn-subtitle= en-abstract= kn-abstract=Several studies have reported the efficacy and safety of polyphenols in human health; however, the verification of their efficacy remains insufficient. The aim of this study was to examine whether fisetin, one of flavonoids prevalently present in fruits and vegetables, could suppress lipopolysaccharide- (LPS-) induced inflammatory responses in macrophages. LPS increased proinflammatory mRNA abundance (MCP 1, IL-1 beta, and iNOS) but were suppressed by fisetin. The increment of nitric oxide by LPS, an oxidative stress factor, was attenuated by fisetin. In addition, LPS-enhanced phosphorylation of mitogen-activated protein kinase (ERK and JNK) was reduced. Finally, fisetin attenuated the expression or activity of uPA, uPAR, MMP-2, and MMP-9, which are known as associated factors of macrophage recruitment or infiltration. In conclusion, fisetin is a promising therapeutic agent for macrophage-related inflammation diseases, like sepsis and atherosclerosis. en-copyright= kn-copyright= en-aut-name=HadaYoshiko en-aut-sei=Hada en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UchidaHaruhito en-aut-sei=Uchida en-aut-mei=Haruhito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= END