Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages.

Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Research Abstract Details 

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Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Abstract Text:

Takashi Ashino,Rieko Yamanaka,Masayuki Yamamoto,Hiroaki Shimokawa,Kenji Sekikawa,Yoichiro Iwakura,Seiji Shioda,Satoshi Numazawa,Takemi Yoshida,Takashi Ashino,Rieko Yamanaka,Masayuki Yamamoto,Hiroaki Shimokawa,Kenji Sekikawa,Yoichiro Iwakura,Seiji Shioda,Satoshi Numazawa,Takemi Yoshida,

Heme oxygenase-1 (HO-1) is induced under infectious diseases in macrophages. We performed experiments using various gene deficient mouse-derived macrophages to determine a detailed induction mechanism of HO-1 by lipopolysaccharide (LPS) and the functional role of HO-1 induction in macrophages. LPS (1mug/mL) maximally induced inducible nitric oxide synthase (iNOS) and HO-1 mRNAs in wild-type (WT) macrophages at 6h and 12h after treatment, respectively, and liberated tumor necrosis factor alpha (TNFalpha) from WT macrophages. LPS also induced iNOS and HO-1 in TNFalpha(-/-) macrophages, but not in iNOS(-/-) macrophages. Interestingly, although LPS strongly induced iNOS, it failed to induce HO-1 almost completely in nuclear-factor erythroid 2-related factor 2 (Nrf2)(-/-) macrophages. The LPS-induced iNOS gene expression was suppressed by pretreatment with HO-1 inducers, hemin and Co-protoporphyrin (CoPP), but not with HO-1 inhibitor, Sn-protoporphyrin in WT macrophages. In the Nrf2(-/-) macrophages, the ability of CoPP to induce HO-1 and its inhibitory effect on the LPS-induced iNOS gene expression were lower than seen in WT macrophages. The present findings suggest that HO-1 is induced via NO-induced nuclear translocation of Nrf2, and the enzymatic function of HO-1 inhibits the overproduction of NO in macrophages.

Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Publishing Authors By Initials

T Ashino,R Yamanaka,M Yamamoto,H Shimokawa,K Sekikawa,Y Iwakura,S Shioda,S Numazawa,T Yoshida,T Ashino,R Yamanaka,M Yamamoto,H Shimokawa,K Sekikawa,Y Iwakura,S Shioda,S Numazawa,T Yoshida,

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Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular immunology

VOLUME: 45

Page Numbers: 2106-15

Journal Abbreviation: Mol. Immunol.

ISSN: 0161-5890

DAY: 19

MONTH: 11

YEAR: 2007

Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. Information

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LANGUAGE: eng

NlmUniqueID: 7905289

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Grant and Affiliation Information for Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages.

AFFILIATION: Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

Country: England

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MEDLINETA: Mol Immunol

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