advertisement
Abstract #13344 Published in IGR 8-1
Prostaglandin E2 induces cyclooxygenase-2 expression in human non-pigmented ciliary epithelial cells through activation of p38 and p42/44 mitogen-activated protein kinases
Rosch S; Ramer R; Brune K; Hinz BBiochemical and Biophysical Research Communications 2005; 338: 1171-1178
Prostaglandins (PGs) have been implicated in lowering intraocular pressure (IOP). A possible role of cyclooxygenase-2 (COX-2) in this process was emphasized by findings showing impaired COX-2 expression in the non-pigmented ciliary epithelium (NPE) of patients with primary open-angle glaucoma. The present study investigates the effect of the major COX-2 product, PGE2 , on the expression of its synthesizing enzyme in human NPE cells (ODM-2). PGE(2 led to an increase of COX-2 mRNA and protein expression, whereas the expression of COX-1 remained unchanged. Upregulation of COX-2 expression by PGE2 was accompanied by time-dependent phosphorylations of p38 mitogen-activated protein kinase (MAPK) and p42/44 MAPK, and was abrogated by inhibitors of both pathways. Moreover, PGE2 -induced COX-2 expression was suppressed by the intracellular calcium chelator, BAPTA/AM, and the protein kinase C inhibitor bisindolylmaleimide II, whereas the protein kinase A inhibitor H-89 was inactive in this respect. Induction of COX-2 expression was also elicited by butaprost (EP2 receptor agonist) and 11-deoxy PGE1 (EP2 /EP4 receptor agonist), but not by EP1 /EP3 receptor agonists (17-phenyl-omega-trinor PGE2 , sulprostone). Consistent with these findings, the EP1 /EP2 receptor antagonist, AH-6809, and the selective EP4 -receptor antagonist, ONO-AE3-208, significantly reduced PGE2 -induced COX-2 expression. Collectively, our results demonstrate that PGE2 at physiologically relevant concentrations induces COX-2 expression in human NPE cells via activation of EP2 - and EP4 receptors and phosphorylation of p38 and p42/44 MAPKs. Positive feedback regulation of COX-2 may contribute to the production of outflow-facilitating PGs and consequently to regulation of IOP.
Dr. S. Rosch, Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany
Classification:
2.9 Ciliary body (Part of: 2 Anatomical structures in glaucoma)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)
