IFN-γ Activates cAMP/PKA/CREB Signaling Pathway in Murine Peritoneal Macrophages

L Liu, Y Wang, Y Fan, CL Li… - Journal of interferon & …, 2004 - liebertpub.com
L Liu, Y Wang, Y Fan, CL Li, ZL Chang
Journal of interferon & cytokine research, 2004liebertpub.com
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 …
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.
Mary Ann Liebert