Reference - Detail
| RRC ID | 6052 |
|---|---|
| Author | Ashino T, Yamanaka R, Yamamoto M, Shimokawa H, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T. |
| Title | Negative feedback regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene expression by heme oxygenase-1 induction in macrophages. |
| Journal | Mol Immunol |
| Abstract |
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 (1 microg/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. |
| Volume | 45(7) |
| Pages | 2106-15 |
| Published | 2008-4-1 |
| DOI | 10.1016/j.molimm.2007.10.011 |
| PII | S0161-5890(07)00805-X |
| PMID | 18022235 |
| MeSH | Animals Cytokines / metabolism Enzyme Induction / drug effects Feedback, Physiological / drug effects* Gene Expression Regulation, Enzymologic / drug effects* Heme Oxygenase-1 / biosynthesis* I-kappa B Proteins / metabolism Inflammation Mediators / metabolism Lipopolysaccharides / pharmacology* Macrophages / drug effects* Macrophages / enzymology* Macrophages / metabolism Metalloporphyrins / pharmacology Mice Mice, Inbred C57BL NF-E2-Related Factor 2 / metabolism NF-KappaB Inhibitor alpha Nitric Oxide Synthase Type II / deficiency Nitric Oxide Synthase Type II / genetics* Phosphorylation / drug effects Protoporphyrins / pharmacology Time Factors Tumor Necrosis Factor-alpha / deficiency |
| IF | 3.641 |
| Times Cited | 79 |
| WOS Category | IMMUNOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
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| The most frequently cited source | News |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC01390 |