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

Rogers LM, Thelen T, Fordyce K, Bourdonnay E, Lewis C, Yu H, Zhang J, Xie J, Serezani CH, Peters-Golden M, Aronoff DM
Am J Reprod Immunol. 2014 71 (1): 34-43

PMID: 23902376 · PMCID: PMC3864121 · DOI:10.1111/aji.12153

PROBLEM - Clostridium sordellii causes endometrial infections, but little is known regarding host defenses against this pathogen.

METHOD OF STUDY - We tested the hypothesis that the immunoregulatory lipid prostaglandin (PG) E2 suppresses human macrophage clearance of C. sordellii through receptor-induced increases in intracellular cyclic adenosine monophosphate (cAMP). The THP-1 macrophage cell line was used to quantify C. sordellii phagocytosis.

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.

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

© 2013 John Wiley & Sons Ltd.

MeSH Terms (14)

Cell Line Clostridium Infections Clostridium sordellii Cyclic AMP Cyclic AMP-Dependent Protein Kinases Dinoprostone Humans Immune Tolerance Immunity, Innate Macrophages Phagocytosis Protein Isoforms Receptors, Prostaglandin E, EP2 Subtype Receptors, Prostaglandin E, EP4 Subtype

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