Role of innate immune response in liver regeneration.
Liver regeneration following partial hepatectomy (PH) requires several steps including innate immune responses, particularly interleukin-6 (IL-6) and tumor necrosis factor-(TNF-)alpha 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-alpha/IL-6 by and activation of NF-kappaB 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-kappaB activation and IL-6 production after PH. In conclusion, the TLR/MyD88 pathway is essential for liver restoration after PH, particularly its early phase.
Iimuro
Yuji
Y
First Department of Surgery and Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan.
Seki
Ekihiro
E
Son
Gakuhei
G
Tsutsui
Hiroko
H
Nakanishi
Kenji
K
Fujimoto
Jiro
J
D000818:Animals; D015152:Blotting, Northern; D004247:DNA / Q000096:biosynthesis; D006498:Hepatectomy; D015850:Interleukin-6 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000378:metabolism; D008115:Liver Regeneration / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis; D010766:Phosphorylation; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D015850:Interleukin-6; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D004247:DNA