EP4 and EP2 receptor activation of protein kinase A by prostaglandin E2 impairs macrophage phagocytosis of Clostridium sordellii

前列腺素 E2 激活蛋白激酶 A 的 EP4 和 EP2 受体会损害巨噬细胞对梭菌的吞噬作用

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作者:Lisa M Rogers, Tennille Thelen, Krystle Fordyce, Emilie Bourdonnay, Casey Lewis, Han Yu, Junyong Zhang, Jingli Xie, Carlos H Serezani, Marc Peters-Golden, David M Aronoff

Conclusion

The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii.

Results

PGE2 increased cAMP levels, activated protein kinase A (PKA), and inhibited the class A scavenger receptor-dependent phagocytosis of C. sordellii. Activation of the EP2 and EP4 receptors increased intracellular cAMP and inhibited phagocytosis, with evidence favoring a more important role for EP4 over EP2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform RI appeared to be more important than RII in mediating the suppression of ingestion of C. sordellii.

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