TY - JOUR
T1 - Lack of tumor necrosis factor receptor type 1 inhibits liver fibrosis induced by carbon tetrachloride in mice
AU - Sudo, Kaori
AU - Yamada, Yasuhiro
AU - Moriwaki, Hisataka
AU - Saito, Kuniaki
AU - Seishima, Mitsuru
PY - 2005/3/7
Y1 - 2005/3/7
N2 - Chronic liver injury causes liver regeneration, resulting in fibrosis. The proinflammatory cytokine tumor necrosis factor (TNF) is involved in the pathogenesis of many acute and chronic liver diseases. TNF has pleiotropic functions, but its role in liver fibrosis has not been clarified. Chronic repeated injection of CCl4 induces liver fibrosis in mice. We examined whether signaling through TNF receptors was critical for this process, using mice lacking either TNF receptor (TNFR) type 1 or TNFR type 2 to define the pathophysiologic role of TNFR signals in liver fibrosis. Liver fibrosis caused by chronic CCl4 exposure was TNF-dependent; histological fibrosis was seen in wild-type (WT) and TNFR-2 knockout (KO) mice, but not in TNFR-1 KO mice. Furthermore, a marked reduction in procollagen and TGF-β synthesis was observed in TNFR-1 KO mice, which also had little detectable NF-κB, STAT3, and AP1 binding, and reduced levels of liver interleukin-6 (IL-6) mRNA compared to WT and TNFR-2 KO mice. In conclusion, our results indicate the possibility that NF-κB, STAT3, and AP1 binding by signals transduced through TNFR-1 plays an important role in liver fibrosis formation.
AB - Chronic liver injury causes liver regeneration, resulting in fibrosis. The proinflammatory cytokine tumor necrosis factor (TNF) is involved in the pathogenesis of many acute and chronic liver diseases. TNF has pleiotropic functions, but its role in liver fibrosis has not been clarified. Chronic repeated injection of CCl4 induces liver fibrosis in mice. We examined whether signaling through TNF receptors was critical for this process, using mice lacking either TNF receptor (TNFR) type 1 or TNFR type 2 to define the pathophysiologic role of TNFR signals in liver fibrosis. Liver fibrosis caused by chronic CCl4 exposure was TNF-dependent; histological fibrosis was seen in wild-type (WT) and TNFR-2 knockout (KO) mice, but not in TNFR-1 KO mice. Furthermore, a marked reduction in procollagen and TGF-β synthesis was observed in TNFR-1 KO mice, which also had little detectable NF-κB, STAT3, and AP1 binding, and reduced levels of liver interleukin-6 (IL-6) mRNA compared to WT and TNFR-2 KO mice. In conclusion, our results indicate the possibility that NF-κB, STAT3, and AP1 binding by signals transduced through TNFR-1 plays an important role in liver fibrosis formation.
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U2 - 10.1016/j.cyto.2004.11.001
DO - 10.1016/j.cyto.2004.11.001
M3 - Article
C2 - 15760680
AN - SCOPUS:14744276371
VL - 29
SP - 236
EP - 244
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 5
ER -