start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=1 article-no= start-page=66 end-page=74 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20161122 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers en-subtitle= kn-subtitle= en-abstract= kn-abstract= Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg. en-copyright= kn-copyright= en-aut-name=LeeSuni en-aut-sei=Lee en-aut-mei=Suni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuzakiHidenori en-aut-sei=Matsuzaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MaedaMegumi en-aut-sei=Maeda en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamamotoShoko en-aut-sei=Yamamoto en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=Kumagai-TakeiNaoko en-aut-sei=Kumagai-Takei en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HatayamaTamayo en-aut-sei=Hatayama en-aut-mei=Tamayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaMiho en-aut-sei=Ikeda en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YoshitomeKei en-aut-sei=Yoshitome en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NishimuraYasumitsu en-aut-sei=Nishimura en-aut-mei=Yasumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=OtsukiTakemi en-aut-sei=Otsuki en-aut-mei=Takemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=2 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=3 en-affil=Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology kn-affil= affil-num=4 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=8 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=9 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=10 en-affil=Department of Hygiene, Kawasaki Medical School kn-affil= END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=3 article-no= start-page=877 end-page=886 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160630 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Actin bundling by dynamin 2 and cortactin is implicated in cell migration by stabilizing filopodia in human non-small cell lung carcinoma cells en-subtitle= kn-subtitle= en-abstract= kn-abstract= The endocytic protein dynamin participates in the formation of actin-based membrane protrusions such as podosomes, pseudopodia, and invadopodia, which facilitate cancer cell migration, invasion, and metastasis. However, the role of dynamin in the formation of actin-based membrane protrusions at the leading edge of cancer cells is unclear. In this study, we demonstrate that the ubiquitously expressed dynamin 2 isoform facilitates cell migration by stabilizing F-actin bundles in filopodia of the lung cancer cell line H1299. Pharmacological inhibition of dynamin 2 decreased cell migration and filopodial formation. Furthermore, dynamin 2 and cortactin mostly colocalized along F-actin bundles in filopodia of serum-stimulated H1299 cells by immunofluorescent and immunoelectron microscopy. Knockdown of dynamin 2 or cortactin inhibited the formation of filopodia in serum-stimulated H1299 cells, concomitant with a loss of F-actin bundles. Expression of wild-type cortactin rescued the punctate-like localization of dynamin 2 and filopodial formation. The incubation of dynamin 2 and cortactin with F-actin induced the formation of long and thick actin bundles, with these proteins colocalizing at F-actin bundles. A depolymerization assay revealed that dynamin 2 and cortactin increased the stability of F-actin bundles. These results indicate that dynamin 2 and cortactin participate in cell migration by stabilizing F-actin bundles in filopodia. Taken together, these findings suggest that dynamin might be a possible molecular target for anticancer therapy. en-copyright= kn-copyright= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakedaTetsuya en-aut-sei=Takeda en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MichiueHiroyuki en-aut-sei=Michiue en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AbeTadashi en-aut-sei=Abe en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakeiKohji en-aut-sei=Takei en-aut-mei=Kohji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neuroscience, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=50 cd-vols= no-issue=6 article-no= start-page=2024 end-page=2032 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure en-subtitle= kn-subtitle= en-abstract= kn-abstract= We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity. en-copyright= kn-copyright= en-aut-name=MaedaMegumi en-aut-sei=Maeda en-aut-mei=Megumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ChenYing en-aut-sei=Chen en-aut-mei=Ying kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LeeSuni en-aut-sei=Lee en-aut-mei=Suni kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=Kumagai-TakeiNaoko en-aut-sei=Kumagai-Takei en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YoshitomeKei en-aut-sei=Yoshitome en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MatsuzakiHidenori en-aut-sei=Matsuzaki en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoShoko en-aut-sei=Yamamoto en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HatayamaTamayo en-aut-sei=Hatayama en-aut-mei=Tamayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaMiho en-aut-sei=Ikeda en-aut-mei=Miho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishimuraYasumitsu en-aut-sei=Nishimura en-aut-mei=Yasumitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OtsukiTakemi en-aut-sei=Otsuki en-aut-mei=Takemi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology kn-affil= affil-num=2 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=3 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=4 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=5 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=6 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=7 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=8 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=9 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=10 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= affil-num=11 en-affil= Department of Hygiene, Kawasaki Medical School kn-affil= END start-ver=1.4 cd-journal=joma no-vol=49 cd-vols= no-issue=2 article-no= start-page=499 end-page=508 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=20160531 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=TGF-β in jaw tumor fluids induces RANKL expression in stromal fibroblasts en-subtitle= kn-subtitle= en-abstract= kn-abstract= Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-β (TGF-β), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-κB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1α (IL-1α) signaling and non-COX-2/PGE2 pathway through TGF-β receptor signaling. TGF-β1 and IL-1α produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma. en-copyright= kn-copyright= en-aut-name=YamadaChiaki en-aut-sei=Yamada en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=AikawaTomonao en-aut-sei=Aikawa en-aut-mei=Tomonao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OkunoEmi en-aut-sei=Okuno en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyagawaKazuaki en-aut-sei=Miyagawa en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AmanoKatsuhiko en-aut-sei=Amano en-aut-mei=Katsuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahataSosuke en-aut-sei=Takahata en-aut-mei=Sosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KimataMasaaki en-aut-sei=Kimata en-aut-mei=Masaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkuraMasaya en-aut-sei=Okura en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IidaSeiji en-aut-sei=Iida en-aut-mei=Seiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KogoMikihiko en-aut-sei=Kogo en-aut-mei=Mikihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=3 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=4 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=5 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=6 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=7 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=8 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= affil-num=9 en-affil=Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University kn-affil= END