Details

Autor(en) / Beteiligte

• Hinz, Burkhard
• Rösch, Susanne
• Ramer, Robert
• Tamm, Ernst R
• Brune, Kay

Titel

Latanoprost induces matrix metalloproteinase-1 expression in human nonpigmented ciliary epithelial cells through a cyclooxygenase-2-dependent mechanism

Ist Teil von

• The FASEB journal, 2005-11, Vol.19 (13), p.1929-1931

Ort / Verlag

United States: Federation of American Societies for Experimental Biology

Erscheinungsjahr

2005

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• ABSTRACTProstaglandins (PGs) have been implicated in the regulation of intraocular pressure (IOP) by facilitating the remodeling of tissues involved in aqueous humor outflow. A contribution of cyclooxygenase‐2 (COX‐2)‐dependent PGs to this process was emphasized by a recent study showing an impaired COX‐2 expression in the nonpigmented ciliary epithelium (NPE) of patients with primary open‐angle glaucoma. With the use of human NPE cells (ODM‐2), the present study therefore investigated the effect of the antiglaucomatous drug latanoprost (PGF2α analog) on the expression of COX‐2 and its association with the induction of matrix metalloproteinases (MMPs). In NPE cells, latanoprost led to a concentration‐ and time‐dependent increase of COX‐2 mRNA levels. Up‐regulation of COX‐2 expression was accompanied by phosphorylations of p38 mitogen‐activated protein kinase (MAPK) and p42/44 MAPK and was abrogated by specific inhibitors of both pathways. PGE2 formation by latanoprost was abolished by the selective COX‐2 inhibitor NS‐398 and by the F‐prostaglandin receptor antagonist AL‐8810. Moreover, latanoprost led to a delayed up‐regulation of MMP‐1 mRNA, whereas the expression of MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2 remained unchanged. Latanoprost‐induced MMP‐1 mRNA and protein expression was abolished by NS‐398 and by COX‐2‐silencing small‐interfering RNA. In line with this finding, MMP‐1 expression was also induced by PGE2, a major COX‐2 product. As a whole, our results show that MMP‐1 expression by latanoprost requires prior up‐regulation of COX‐2. Induction of COX‐2‐ and subsequent MMP‐1 expression in the NPE may represent a potential mechanism underlying the IOP‐lowering and antiglaucomatous action of latanoprost.