Activation of prostaglandin e2 -ep4 signaling reduces chemokine production in adipose tissue

Eva H.C. Tang, Yin Cai, Chi Kin Wong, Viviane Z. Rocha, Galina K. Sukhova, Koichi Shimizu, Ge Xuan, Paul M. Vanhoutte, Peter Libby, Aimin Xu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

22 Citations (Scopus)


Infl ammation of adipose tissue induces metabolic derangements associated with obesity. Thus, determining ways to control or inhibit infl ammation in adipose tissue is of clinical interest. The present study tested the hypothesis that in mouse adipose tissue, endogenous prostaglandin E2 (PGE2 ) negatively regulates infl ammation via activation of prostaglandin E receptor 4 (EP4) . PGE2 (5-500nM) attenuated lipopolysaccharide-induced mRNA and protein expression of chemokines, including interferon- γ -inducible protein 10 and macrophage-inflammatory protein-1α in mouse adipose tissue. A selective EP4 antagonist (L161,982) reversed, and two structurally different selective EP4 agonists [CAY10580 and CAY10598] mimicked these actions of PGE2 . Adipose tissue derived from EP4- defi cient mice did not display this response. These fi ndings establish the involvement of EP4 receptors in this antiinfl ammatory response. Experiments performed on adipose tissue from high-fat-fed mice demonstrated EP4-dependent attenuation of chemokine production during diet-induced obesity. The anti-infl ammatory actions of EP4 became more important on a high-fat diet, in that EP4 activation suppressed a greater variety of chemokines. Furthermore, adipose tissue and systemic infl ammation was enhanced in high-fat-fed EP4-defi cient mice compared with wild-type littermates, and in high-fat-fed untreated C57BL/6 mice compared with mice treated with EP4 agonist. These fi ndings provide in vivo evidence that PGE2 -EP4 signaling limits infl ammation. In conclusion, PGE2 , via activation of EP4 receptors, functions as an endogenous anti-infl ammatory mediator in mouse adipose tissue, and targeting EP4 may mitigate adipose tissue infl ammation. -Tang, E. H. C., Y. Cai, C. K. Wong, V. Z. Rocha, G. K. Sukhova, K. Shimizu, G. Xuan, P. M. Vanhoutte, P. Libby, and A. Xu. Activation of prostaglandin E2 -EP4 signaling reduces chemokine production in adipose tissue. J. Lipid Res . 2015.

Original languageEnglish
Pages (from-to)358-368
Number of pages11
JournalJournal of Lipid Research
Issue number2
Early online date15 Dec 2014
Publication statusPublished - Feb 2015
Externally publishedYes


  • Chemokines
  • Eicosanoids
  • EP4 receptor
  • Fat
  • Prostanoids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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