MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis

Keisuke Ojiro, Hirotoshi Ebinuma, Nobuhiro Nakamoto, Kanji Wakabayashi, Yohei Mikami, Yuichi Ono, Chu Po-Sung, Shingo Usui, Rumiko Umeda, Hiromasa Takaishi, Yoshiyuki Yamagishi, Hidetsugu Saito, Takanori Kanai, Toshifumi Hibi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We have explored the pathological role of the MyD88 signaling pathway via Toll-like receptors (TLRs) that mediate the recognition of pathogen-associated molecular patterns (PAMPs) in a murine model of autoimmune hepatitis induced by administering Concanavalin A (ConA). We first found that various TLRs and MyD88 molecules were expressed in liver of Con A-treated and untreated wild-type (WT) mice including liver macrophages. Flowcytometric analysis revealed that liver CD11b+CD11c- and CD11b+CD11c+ antigen-presenting cells express TLR2, although NK and NKT cells did not. When WT and MyD88-/- mice were intravenously administered with Con A, the severity of hepatitis was significantly lower in Con A-injected MyD88-/- mice than in WT mice in terms of the histopathology, the levels of serum transaminase and pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-6), and upregulation of CD80/CD86 and TNF-α on/in liver macrophages. The results provide evidence of a possible contribution of the TLRs-MyD88 signaling pathway in activating TLR-expressing liver macrophages in the autoimmune hepatitis model, and thus indicate that the strategy of blockade of pathological pathogens via the intestinal lumen may be feasible for the treatment of the disease.

Original languageEnglish
Pages (from-to)744-749
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume399
Issue number4
DOIs
Publication statusPublished - 2010 Sep 1

Keywords

  • Concanavalin A
  • Hepatitis
  • Macrophage
  • MyD88
  • Toll-like receptors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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