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Role of innate immune response in liver regeneration
Author(s) -
Iimuro Yuji,
Seki Ekihiro,
Son Gakuhei,
Tsutsui Hiroko,
Nakanishi Kenji,
Fujimoto Jiro
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04651.x
Subject(s) - innate immune system , tlr2 , liver regeneration , microbiology and biotechnology , tumor necrosis factor alpha , toll like receptor , signal transduction , immune system , immunology , tlr4 , receptor , biology , medicine , regeneration (biology)
Liver regeneration following partial hepatectomy (PH) requires several steps including innate immune responses, particularly interleukin‐6 (IL‐6) and tumor necrosis factor‐(TNF‐)α production by Kupffer cells, although the activation processes are still unknown. Toll‐like receptors (TLR) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLR. When the receptors are activated, cells bearing TLR produce various pro‐nflammatory cytokines in a MyD88‐dependent manner. The authors investigated whether TLR/MyD88 signaling is critical for induction of innate immune responses after PH. In Myd88 ‐/‐ mice after PH, induction of expression of immediate early genes involved in hepatocyte replication and phosphorylation of signal transducer and activators of transcription 3 (STAT3) in the liver, and production of TNF‐α/IL‐6 by and activation of NF‐κB in the Kupffer cells were grossly subnormal and were associated with impaired liver regeneration, while TLR2, 4 and 9, which recognize Gram‐negative and ‐positive bacterial products, are not essential for NF‐κB activation and IL‐6 production after PH. In conclusion, the TLR/MyD88 pathway is essential for liver restoration after PH, particularly its early phase.