cAMP levels regulate macrophage alternative activation marker expression

The capacity for macrophages to polarize into distinct functional activation states (e.g., M1, M2) is critical to tune an inflammatory response to the relevant infection or injury. Alternative or M2 polarization of macrophages is most often achieved in vitro in response to IL-4/IL-13 and results in the transcriptional up-regulation of a constellation of characteristic M2 marker genes. In vivo, additional signals from the inflammatory milieu can further increase or decrease M2 marker expression. Particularly, activation of cAMP-generating G protein-coupled receptors is reported to increase M2 markers, but whether this is strictly dependent upon cAMP production is unclear. We report herein that increased cAMP alone can increase IL-4-dependent M2 marker expression through a PKA/C/EBP beta/CREB dependent pathway in murine macrophages.

Automated summary

The capacity for macrophages to polarize into distinct functional activation states is critical for tuning inflammatory responses. In addition to IL-4/IL-13, signals from the inflammatory milieu can further modulate M2 marker expression, with cAMP playing a role in increasing M2 markers through a PKA/C/EBP beta/CREB dependent pathway.