Interferon-gamma and transforming growth factor-beta modulate the activation of mitogen-activated protein kinases and tumor necrosis factor-alpha production induced by Fc gamma-receptor stimulation in murine macrophages.
Engagement of receptors for the Fc region of IgG (Fc gamma R) can activate a variety of biological responses in macrophages, and these responses can be modulated either positively or negatively by co-stimulation with a variety of agents including cytokines such as interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). We have previously demonstrated that Fc gamma R crosslinking activates the mitogen-activated protein kinase (MAPK) family members p42MAPK, p38, and JNK. Herein, we examined the modulatory effect of IFN-gamma, TGF-beta, and platelet-activating factor (PAF) on Fc gamma R-induced MAPK activation in murine macrophages. Fc gamma R-induced activation of p42MAPK and JNK was augmented nearly two-fold by pretreatment with IFN-gamma. Conversely, TGF-beta pretreatment suppressed Fc gamma R-induced activation of p42MAPK, JNK, and p38. These modulatory effects of IFN-gamma and TGF-beta on MAPK activation correlated with changes in Fc gamma R-stimulated TNF-alpha production by these two cytokines.
Rose
D M
DM
Division of Basic Sciences, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Winston
B W
BW
Chan
E D
ED
Riches
D W
DW
Henson
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
D000911:Antibodies, Monoclonal; D017452:Receptors, IgG; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017871:Calcium-Calmodulin-Dependent Protein Kinases