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 Fe 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 p42(MAPK), 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 p42(MAPK) and JNK was augmented nearly two-fold by pretreatment with IFN-gamma. Conversely, TGF-beta pretreatment suppressed Fc gamma R-induced activation of p42(MAPK), 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. (C) 1997 Academic Press.