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

Takiko Oguro, Yuko Takahashi, Takashi Ashino, Atsushi Takaki, Seiji Shioda, Reiko Horai, Masahide Asano, Kenji Sekikawa, Yoichiro Iwakura, Takemi Yoshida

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)63-66
Number of pages4
JournalFEBS Letters
Volume516
Issue number1-3
DOIs
Publication statusPublished - Apr 10 2002

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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