Transforming growth factor beta differentially modulates the inducible nitric oxide synthase gene in distinct cell types.
Nitric oxide is a mediator of paracrine cell signalling. An inducible form of nitric oxide synthase (iNOS) is expressed in macrophages and in Swiss 3T3 cells. Transforming growth factor beta (TGF-beta) is a cytokine that modulates many cellular functions. We find that TGF-beta cannot induce iNOS mRNA expression, either in macrophage cell lines or in Swiss 3T3 cells. However, TGF-beta attenuates lipopolysaccharide induction of iNOS mRNA in macrophages. In contrast, TGF-beta enhances iNOS induction by phorbol ester, serum or lipopolysaccharide in 3T3 cells. Thus TGF-beta can inhibit or augment iNOS mRNA induction in response to primary inducers, depending on the cell type in question.
Gilbert
R S
RS
Department of Biological Chemistry, UCLA School of Medicine 90024.
Herschman
H R
HR
D016475:3T3 Cells; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005796:Genes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases