title: Involvement of tumor necrosis factor alpha, rather than interleukin-1alpha/beta or nitric oxides in the heme oxygenase-1 gene expression by lipopolysaccharide in the mouse liver.
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-1beta (IL-1beta), rather than other inflammatory cytokines in the mouse liver. However, we found that IL-1alpha/beta 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 alpha KO (TNFalphaKO) 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 TNFalphaKO. In addition, the phosphorylation of c-JUN N-terminal kinase (JNK) and p38, but not extracellular signal-regulated kinase, was very low in TNFalphaKO mice due to LPS administration. All of these findings indicate that TNFalpha 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.
authors.affiliation: Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, 142-8555, Tokyo, Japan.
authors.forename: Takiko
authors.initials: T
authors.lastname: Oguro
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ashino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Kenji
authors.initials: K
authors.lastname: Sekikawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Takemi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D008565:Membrane Proteins; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008668:Metallothionein; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases