title: TNFR1-mediated signaling is important to induce the improvement of liver fibrosis by bone marrow cell infusion.
abstract: The importance of TNF-α signals mediated by tumor necrosis factor receptor type 1 (TNFR1) in inflammation and fibrosis induced by carbon tetrachloride (CCl(4)), and in post-injury liver regeneration including a GFP/CCl(4) model developed as a liver repair model by bone marrow cell (BMC) infusion, was investigated. In mice in which TNFR1 was suppressed by antagonist administration or by knockout, liver fibrosis induced by CCl(4) was significantly decreased. In these mice, intrahepatic macrophage infiltration and TGF-β1 expression were reduced and stellate cell activity was decreased; however, expression of MMP-9 was also decreased. With GFP-positive BMC (TNFR1 wild-type, WT) infusion in these mice, fibrosis proliferation, including host endogenous intrahepatic macrophage infiltration, TGF-β1 expression and stellate cell activity, increased significantly. There was no significant increase of MMP-9 expression. In this study, TNFR1 in hosts had a promoting effect on CCl(4)-induced hepatotoxicity and fibrosis, whereas BMC infusion in TNFR1 knockout mice enhanced host-derived intrahepatic inflammation and fibrosis proliferation. These findings differed from those in WT recipient mice, in which improvement in inflammation and fibrosis with BMC infusion had previously been reported. TNFR1-mediated signaling might be important to induce the improvement of liver fibrosis by bone marrow cell infusion.
authors: Department of Gastroenterology & Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Takuro
authors: T
authors: Hisanaga
authors: Shuji
authors: S
authors: Terai
authors: Takuya
authors: T
authors: Iwamoto
authors: Taro
authors: T
authors: Takami
authors: Naoki
authors: N
authors: Yamamoto
authors: Tomoaki
authors: T
authors: Murata
authors: Toshifumi
authors: T
authors: Matsuyama
authors: Hiroshi
authors: H
authors: Nishina
authors: Isao
authors: I
authors: Sakaida
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse