“Macrophage” nitric oxide synthase is a glucocorticoid-inhibitable primary response gene in 3T3 cells

✍ Scribed by Rebecca S. Gilbert; Harvey R. Herschman

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 523 KB
• Volume: 157
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041570117

✦ Synopsis

Both nitric oxide and prostaglandins are potent paracrine mediators of intercellular communication. An endotoxin-lipopolysaccharide (LPS) inducible form of nitric oxide synthase (mac-NOS) has recently been cloned from murine macrophages. An inducible prostaglandin synthase (TI51 O/PGS-2), cloned from 3T3 cells, is also induced in LPS-activated macrophage. Because of the wide range of ligands that induce primary response genes in 3T3 cells, the ease of studying chimeric promoter constructs in 3T3 cells, and the importance of both nitric oxide and prostaglandins as paracrine mediators, we examined expression of mac-NOS in 3T3 cells. Tetradecanoyl phorbol-13-acetate (TPA), forskolin, platelet-derived growth factor, fibroblast growth factor, and serum all induce mac-NOS expression in Swiss 3T3 cells. Thus the mac-NOS gene can respond to a far wider range of inducers than previously suspected. mac-NOS is a primary response gene; cycloheximide does not block induction. TPA-induced mac-NOS and TlSl OIPGS-2 mRNA accumulation patterns are similar. LPS is a potent inducer of mac-NOS in Swiss 3T3 cells but cannot induce TISlO/PGS-2. In contrast, v-src expression induces TlSlO/PCS-2 message, but not iNOS message in a BALBIc 3T3 cell line containing a temperature-sensitive v-src gene. Dexamethasone (DEX) prevents induction of TlSl OIPGS-2, but not most other primary response genes. DEX also blocks mac-NOS induction in Swiss 3T3 cells. The inducible TlSlOIPGS-2 and mac-NOS genes, responsible for the production of two distinct paracrine agents, appear to share many regulatory features in 3T3 cells.