Abstract
Interferon-γ (IFN-γ) is a macrophage-activating cytokine that serves critical functions in innate and adaptive immunity and is thought to be mediated by the Jak-Stat signaling pathway. The present study establishes for the first time that cyclic adenosine monophosphate, protein kinase A, and cAMP response element-binding protein (cAMP/PKA/CREB) are coregulators of the IFN-γ signaling pathway. Experimental data indicate that exogenous IFN-γ stimulated cAMP accumulation and PKA activation in time-dependent and dose-dependent manners in murine peritoneal macrophages. Moreover, IFN-γ stimulated CREB phosphorylation and CREB DNA binding, which could be significantly attenuated by PKA inhibition with H89. It appears that a novel cAMP/PKA/CREB signaling pathway is activated by IFN-γ in macrophages, suggesting that an alternate signaling pathway exists in macrophages in response to IFN-γ.
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