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ROLE OF PROSTAGLANDIN TRANSPORTER IN PROSTAGLANDIN E2 INDUCED COLONIC EPITHELIAL BARRIER ALTERATIONS
Author(s) -
Virapin Manigandan Lejeune,
Chadee Kris
Publication year - 2008
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.22.1_supplement.328.10
Subject(s) - prostaglandin e2 receptor , barrier function , receptor , prostaglandin e2 , tight junction , prostaglandin , microbiology and biotechnology , endocrinology , agonist , medicine , stimulation , signal transduction , prostaglandin e , chemistry , biology
Prostaglandin E2 (PGE2) is an important pro‐inflammatory lipid mediator that is produced in excess during inflammatory bowel diseases (IBD). It exerts its action by signaling via four different EP receptor subtypes. In this study, we determine the role of EP4 receptor in the alteration of epithelial barrier functions. Screening for EP4 receptor expression in human colonic resection tissues (IBD patient vs. healthy control) revealed differential receptor expression/localization. EP4 receptors were normally localized on epithelial apical plasma membranes whereas; they were diffusely expressed throughout the cells from patients with IBD. To check how PGE2 is transported across colonic cells towards apical EP4 receptors, we probed for Prostaglandin Transporters (PGT) in human colonic epithelial cells. T84 monolayer modestly expressed PGT protein which increased 2‐fold following TNF‐a stimulation. A corresponding increase in the trans epithelial transport of 3H‐PGE2 was also observed. Moreover, EP4 receptor specific agonist caused a steep decrease in the Trans Epithelial Resistance (TER) of T84 monolayer indicating a loss of barrier function. Alteration in TER is associated with exclusive changes in the localization of a tight junction protein, Claudin4. Taken together, these studies unravel a complex mechanism whereby PGT play role in PGE2 induced alteration of colonic epithelial barrier function.