A pivotal role of IL-12 in Th1-dependent mouse liver injury |
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Authors: | Tanaka Yoshitaka; Takahashi Akiko; Watanabe Kazuhito; Takayama Kiyoshi; Yahata Takashi; Habu Sonoko; Nishimura Takashi |
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Institution: | Department of Immunology, Tokai University School of Medicine, Bohseidai, Isehara 259-11, Japan Research Center, Taisho Pharmaceutical Co., Ltd Ohmiya 330, Japan |
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Abstract: | Intravenous injection of Proplonibacterium acnes and llpopolysaccharide(LPS) with a 7 day interval caused CD4+ T cell-dependent severeliver injury in the C57BL/6 (H-2b) mouse strain. In contrast,BALB/c (H-2d mice were resistant to P. acnes and LPS-inducedliver injury. The different susceptibilities of the two mousestrains to liver injury appeared to be closely correlated withtheir different abilities to produce IFN- after P. acnea priming.Namely, the sensitive C57BL/6 mouse strain produced a significantlevel of IFN- 7–10 days after P. acnes injection, whereasno significant amount of serum IFN- was detected in the resistantBALB/c mouse strain. The important role of IFN- in liver injurywas demonstrated from the finding that In vivo administrationof anti-IFN- mAb abrogated P. acnes and LPS-induced liver injuryin C57BL/6 mice. Moreover, it was demonstrated that In vivoadministration of recombinant IL-12, a key cytokine for theinduction of IFN- , into mice induced P. acnes and LPS-inducedliver injury in the resistant BALB/c mouse strain. Conversely,In vivo administration of anti-IL-12 mAb blocked the developmentof liver injury in the sensitive C57BL/6 mouse strain. Moreover,it was demonstrated that the failure of the induction of liverinjury in BALB/c mice appeared to be derived from the lack ofexpression of IL-12 at the local site of liver in P. acnes-prlmedmice. These results strongly indicated that endogenous IL-12,which stimulates Th 1-dominant cellular immunity and IFN- production,may be an essential cytokine on the course of T cell-dependentliver injury. |
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Keywords: | IL-12 liver injury Th1 |
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