Lack of tumor necrosis factor receptor type 1 inhibits liver fibrosis induced by carbon tetrachloride in mice

Kaori Sudo, Yasuhiro Yamada, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)236-244
Number of pages9
JournalCytokine
Volume29
Issue number5
DOIs
Publication statusPublished - 07-03-2005
Externally publishedYes

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Receptors, Tumor Necrosis Factor, Type I
Carbon Tetrachloride
Tumor Necrosis Factor Receptors
Liver Cirrhosis
Liver
Knockout Mice
Tumor Necrosis Factor-alpha
Fibrosis
Procollagen
Liver Regeneration
Liver Diseases
Interleukin-6
Chronic Disease
Cytokines
Messenger RNA
Injections

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Sudo, Kaori ; Yamada, Yasuhiro ; Moriwaki, Hisataka ; Saito, Kuniaki ; Seishima, Mitsuru. / Lack of tumor necrosis factor receptor type 1 inhibits liver fibrosis induced by carbon tetrachloride in mice. In: Cytokine. 2005 ; Vol. 29, No. 5. pp. 236-244.
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Lack of tumor necrosis factor receptor type 1 inhibits liver fibrosis induced by carbon tetrachloride in mice. / Sudo, Kaori; Yamada, Yasuhiro; Moriwaki, Hisataka; Saito, Kuniaki; Seishima, Mitsuru.

In: Cytokine, Vol. 29, No. 5, 07.03.2005, p. 236-244.

Research output: Contribution to journalArticle

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