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/EBPβ/CREB dependent pathway in murine macrophages.

巨噬细胞极化成不同功能激活状态（例如，M1、M2）的能力对于调节对相关感染或损伤的炎症反应至关重要。巨噬细胞的替代或 M2 极化最常在体外响应 IL-4/IL-13 实现，并导致特征性 M2 标记基因群的转录上调。体内，来自炎症环境的额外信号可以进一步增加或减少 M2 标志物的表达。特别是，据报道激活产生 cAMP 的 G 蛋白偶联受体会增加 M2 标志物，但这是否严格依赖于 cAMP 的产生尚不清楚。我们在此报告，单独增加的 cAMP 可以通过鼠巨噬细胞中的 PKA/C/EBPβ/CREB ​​依赖性途径增加 IL-4 依赖性 M2 标志物的表达。