IFN-gamma selectively inhibits lipopolysaccharide-inducible JE/monocyte chemoattractant protein-1 and KC/GRO/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages.
IFN-gamma and LPS have both been shown to stimulate enhanced chemoattractant cytokine gene expression in mononuclear phagocytes. In this report, IFN-gamma was found to suppress LPS-induced chemokine mRNA expression in a cell type- and gene-specific fashion. Expression of JE (monocyte chemoattractant protein-1) and KC (GRO/melanoma growth-stimulating activity) mRNA in macrophages stimulated with LPS was markedly suppressed by IFN-gamma in a dose- and time-dependent fashion. LPS-induced IP-10 mRNA was unaffected by IFN-gamma under identical experimental conditions. This effect was cell type-specific because JE and KC mRNA expression in LPS-stimulated murine endothelial cells, TNF-alpha-stimulated endothelial cells, and NIH-3T3 cells were unaffected by IFN-gamma. The IFN-gamma-mediated suppression of LPS-stimulated KC mRNA expression was independent of protein synthesis and mediated at the transcriptional level. These observations indicate that IFN-gamma may function as a negative regulatory signal for the expression of some proinflammatory cytokines in macrophages. The cell type-dependent differential behavior of individual members of the chemokine family may be an important determinant of the cellular composition and outcome of an inflammatory response.
Ohmori
Y
Y
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
Hamilton
T A
TA
D000818:Animals; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects
D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma