title: EP4 and EP2 receptor activation of protein kinase A by prostaglandin E2 impairs macrophage phagocytosis of Clostridium sordellii.
abstract: OBJECTIVE
  Clostridium sordellii causes endometrial infections, but little is known regarding host defenses against this pathogen.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rogers
authors.forename: Tennille
authors.initials: T
authors.lastname: Thelen
authors.forename: Krystle
authors.initials: K
authors.lastname: Fordyce
authors.forename: Emilie
authors.initials: E
authors.lastname: Bourdonnay
authors.forename: Casey
authors.initials: C
authors.lastname: Lewis
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.forename: Junyong
authors.initials: J
authors.lastname: Zhang
authors.forename: Jingli
authors.initials: J
authors.lastname: Xie
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Serezani
authors.forename: Marc
authors.initials: M
authors.lastname: Peters-Golden
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
mesh_terms: D002460:Cell Line; D003015:Clostridium Infections / Q000276:immunology*; D047989:Paraclostridium sordellii / Q000276:immunology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology*; D010587:Phagocytosis; D020033:Protein Isoforms / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone
keywords: Abortion; endometritis; innate immunity; phagocytosis; pregnancy; toxic shock syndrome
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