Induction of nitric oxid esynthase(NOS) by soluble glucocorticoid induced tumor necrosis factor receptor(sGITR) is modulated by IFN-g in murine macrophage.
- Author:
Hyun Hee SHIN
1
;
Hyeon Woo LEE
;
Hye Seon CHOI
Author Information
1. Department of Biological Sciences and the Immunomodulation Research Center University of Ulsan, Ulsan 680-749, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
glucocorticoids;
interferon type II;
marophages;
nitric oxide;
nitric-oxide synthase;
receptors, tumor necrosis factor
- MeSH:
Animals;
Cells, Cultured;
Cytokines/*metabolism;
Enzyme Induction;
Interferon Type II/pharmacology;
Macrophages/*enzymology/physiology;
Mice;
NF-kappa B/metabolism;
Nitric Oxide/metabolism;
Nitric-Oxide Synthase/*biosynthesis;
Protein-Tyrosine Kinase/metabolism;
Protein-Tyrosine-Phosphatase/metabolism;
Receptors, Nerve Growth Factor/*metabolism;
Receptors, Tumor Necrosis Factor/*metabolism
- From:Experimental & Molecular Medicine
2003;35(3):175-180
- CountryRepublic of Korea
- Language:English
-
Abstract:
Earlier study showed that glucocorticoid induced tumor necrosis factor receptor (GITR), a new TNFR family, activated murine macrophages to express inducible nitric oxide synthase (iNOS) and to generate nitric oxide (NO). A possible involvement of pro-inflammatory cytokines on NO production by GITR was investigated in vitro systems and signaling molecules contributing to sGITR-induced iNOS production are determined in Raw 264.7 cells, a murine macrophage cell line. The result showed that the synergy was afforded by the combination of GITR with IFN-gamma in a dose-dependent manner but IFN-gamma alone was not able to induce NOS. No effects were observed with TNF-alpha, IL-1beta, or IL-6 co-treated with GITR. To determine signaling molecules contributing to sGITR-induced iNOS production, a specific inhibitor for signal pathway proteins tested showed that PDTC (NF- kB) and genistein (tyrosine kinase) inhibited NOS induction significantly, while sodium orthovanadate (tyrosine phosphatase) potentiated NOS expression. These results suggest that activations of NF-kB were involved in induction of iNOS by GITR and IFN-gamma priming caused earlier and stronger NF-kB activation.
