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

• Published in: FEBS letters 2002-04, Vol.516 (1), p.63-66
• Main Authors: Oguro, Takiko, Takahashi, Yuko, Ashino, Takashi, Takaki, Atsushi, Shioda, Seiji, Horai, Reiko, Asano, Masahide, Sekikawa, Kenji, Iwakura, Yoichiro, Yoshida, Takemi
• Format: Article
• Language: English
• Subjects: c-JUN N-terminal kinase; Cytokine; Extracellular signal-regulated kinase; Gene deficient mouse; Heme oxygenase-1; Interleukin-1; Lipopolysaccharide; Liver; Metallothionein; Nitric oxide; p38; Signal transduction; Tumor necrosis factor α
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02502-4

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.