Premium
Determining the downstream signaling pathways through which prostaglandin E2 inhibits inflammatory mediator output in in human myometrial cells (911.6)
Author(s) -
Levinson Hayley,
Wood Stephen,
Slater Donna
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.911.6
Subject(s) - prostaglandin e2 receptor , prostaglandin e2 , downregulation and upregulation , myometrium , intracellular , signal transduction , receptor , mediator , prostaglandin , chemistry , endocrinology , microbiology and biotechnology , medicine , biology , uterus , gene , agonist , biochemistry
Objective: Prostaglandin E2 (PGE2) represses interleukin‐1β (IL‐1β) induced inflammatory mediator output in human myometrial cells via EP2/4 receptors. Downstream EP2/4 signaling involves upregulation of intracellular cAMP which may activate multiple pathways, including protein kinase A (PKA) and exchange proteins activated by cAMP (Epacs). Methods: Myometrial biopsies from term elective Caesarean deliveries prior to labour onset (n=5, 37‐40 weeks gestation) were used to isolate myometrial cells. PKA and Epac gene expression was assessed by RT‐PCR. Myometrial cells were either non‐treated or stimulated with IL‐1β +/‐ co‐treatment with cAMP analogs to selectively activate PKAI, PKAII, or Epacs. Interleukin‐8 (CXCL8) output was measured by ELISA. Statistical analysis was performed by repeated measures ANOVA followed by a Bonferroni test. Results: Expression of both Epac isoforms and six of seven PKA subunits were identified in isolated myometrial cells. IL‐1β increased CXCL8 output in human myometrial cells (p蠄0.001). Co‐treatment with PKAI or PKAII selective cAMP analogs repressed this response (p蠄0.001). No significant repression was observed when cells were co‐treated with the Epac selective cAMP analog. Conclusions: PGE2 mediated repression of IL‐1β induced inflammatory output in human myometrial cells is mediated in part by PKA, but not Epac, signaling pathways. Grant Funding Source : Supported by Canadian Institutes of Health Research and Alberta Innovates‐Health Solutions