Involvement of tumor necrosis factor α, rather than interleukin‐1α/β or nitric oxides in the heme oxygenase‐1 gene expression by lipopolysaccharide in the mouse liver

FEBS Letters

Sekikawa, Kenji⁴  Yoshida, Takemi²  Oguro, Takiko²  Takaki, Atsushi³  Iwakura, Yoichiro⁵  Asano, Masahide⁵  Takahashi, Yuko²  Horai, Reiko⁵  Shioda, Seiji¹  Ashino, Takashi² 

[1] Department of Anatomy, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan;Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan;Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;Department of Immunology, National Institute of Animal Health, Tsukuba, Ibaraki 305-0856, Japan;Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

关键词: Heme oxygenase-1;    Lipopolysaccharide;    Cytokine;    Interleukin-1;    Tumor necrosis factor α;    Liver;    Gene deficient mouse;    Nitric oxide;    Signal transduction;    c-JUN N-terminal kinase;    p38;    Extracellular signal-regulated kinase;    Metallothionein;   

DOI  :  10.1016/S0014-5793(02)02502-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Heme oxygenase-1 (HO-1) is induced under various oxidative stress conditions, such as lipopolysaccharide (LPS) insult. Induction of HO-1 by LPS is reported to be mediated through interleukin-1β (IL-1β), rather than other inflammatory cytokines in the mouse liver. However, we found that IL-1α/β knockout (KO) mice responded well to LPS insult, as did wild-type mice with respect to HO-1 mRNA induction (about 30-fold increase). In contrast, tumor necrosis factor α KO (TNFαKO) mice responded very weakly to LPS in the HO-1 mRNA expression, but not metallothionein mRNA. Recent studies reveal that nitric oxide from Kupffer cells is involved in HO-1 induction in the liver produced by LPS. Therefore, nitrite and nitrate concentrations in the liver were also measured and these parameters did not increase in either IL-1KO or TNFαKO. In addition, the phosphorylation of c-JUN N-terminal kinase (JNK) and p38, but not extracellular signal-regulated kinase, was very low in TNFαKO mice due to LPS administration. All of these findings indicate that TNFα is a major candidate to trigger HO-1 induction in response to LPS stimulation, and that its message is likely transduced through JNK and p38 pathways.

【 授权许可】

Unknown