Premium
EP4 and EP2 Receptor Activation of Protein Kinase A by Prostaglandin E 2 Impairs Macrophage Phagocytosis of Clostridium sordellii
Author(s) -
Rogers Lisa M.,
Thelen Tennille,
Fordyce Krystle,
Bourdonnay Emilie,
Lewis Casey,
Yu Han,
Zhang Junyong,
Xie Jingli,
Serezani Carlos H.,
PetersGolden Marc,
Aronoff David M.
Publication year - 2014
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12153
Subject(s) - prostaglandin e2 receptor , biology , protein kinase a , receptor , phagocytosis , microbiology and biotechnology , biochemistry , kinase , agonist
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 ) E 2 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 PGE 2 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 EP 2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform R I appeared to be more important than R II in mediating the suppression of ingestion of C. sordellii . Conclusion The endogenous lipid mediator PGE 2 impairs human innate immune responses against C. sordellii .