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Nitric oxide and prostaglandin E 2 participate in lipopolysaccharide/interferon‐γ‐induced heme oxygenase 1 and prevent RAW264.7 macrophages from UV‐irradiation‐induced cell death
Author(s) -
Chen YenChou,
Shen ShingChuan,
Lee WoanRuoh,
Lin HuiYi,
Ko ChingHuai,
Lee Tony J.F.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10230
Subject(s) - heme oxygenase , nitric oxide , lipopolysaccharide , chemistry , prostaglandin e2 , sodium nitroprusside , prostaglandin e , nitric oxide synthase , protein kinase a , heme , microbiology and biotechnology , p38 mitogen activated protein kinases , pharmacology , biochemistry , kinase , immunology , endocrinology , biology , enzyme , organic chemistry
Induction of heme oxygenase (HO)‐1 during inflammation has been demonstrated in many cell types, but the contribution of inflammatory molecules nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) has remained unresolved. Here we show that NO donors including sodium nitroprusside (SNP) and spermine nonoate (SP‐NO), and PGE 2 significantly stimulate HO‐1 expression in RAW264.7 macrophages, associated with alternative induction on NO and PGE 2 in medium, respectively. NO donors also show the inductive effect on cyclo‐oxygenase 2 protein and PGE 2 production. In the presence of lipopolysaccharide and interferon‐γ (LPS/IFN‐γ), HO‐1 protein was induced slightly but significantly, and SNP, SP‐NO, and PGE 2 enhanced HO‐1 protein induced by LPS/IFN‐γ. L ‐Arginine analogs N ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME) and N ‐nitro‐ L ‐arginine (NLA) significantly block HO‐1 protein induced by LPS/IFN‐γ associated with a decrease in NO (not PGE 2 ) production. And, NSAIDs aspirin and diclofenase dose dependently inhibited LPS/IFN‐γ‐induced HO‐1 protein accompanied by suppression of PGE 2 (not NO) production. PD98059 (a specific inhibitor of MEKK), but not SB203580 (a specific inhibitor of p38 kinase), attenuated PGE 2 (not SP‐NO) induced HO‐1 protein. Under UVC (100 J/m 2 ) and UVB (50 J/m 2 ) irradiation, PGE 2 or SP‐NO treatment prevents cells from UVC or UVB‐induced cell death, and HO‐1 inhibitor tin protoporphyrin (SnPP) reverses the preventive effects of PGE 2 and SP‐NO. The protective activity induced by PGE 2 on UVC or UVB irradiation‐induced cell death was blocked by MAPK inhibitor PD98059 (not SB203580). These results demonstrated that inflammatory molecules NO and PGE 2 were potent inducers of HO‐1 gene, and protected cells from UV‐irradiation‐induced cell death through HO‐1 induction. J. Cell. Biochem. 86: 331–339, 2002. © 2002 Wiley‐Liss, Inc.