COX-2 dependent PGE2 downregulates αv integrin expression via the EP3 receptor in cultured mesangial cells

• Published in: Journal of clinical pathology Vol. 57; no. 5; pp. 553 - 555
• Main Authors: Waldner, C, Schrör, K, Heering, P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.05.2004; BMJ; Copyright 2004 Journal of Clinical Pathology
• Subjects: Biological and medical sciences; celecoxib; COX-2; cyclooxygenase 2; EP3 receptor; General aspects; lipopolysaccharide; LPS; Medical sciences; mesangial cell; PGE2; prostaglandin E2; reverse transcriptase polymerase chain reaction; RT-PCR; Short Reports; αv integrins; Cell culture; Enzyme; Mesangial cell; Arachidonic acid derivatives; Cyclooxygenase 2; Cell adhesion molecule; Prostaglandin E2; Kidney; Renal glomerulus; Medicine; Integrin; Urinary system; Eicosanoid; Oxidoreductases; Biological receptor
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2003.013169

Background: In experimental glomerulonephritis, inhibition of cyclooxygenase 2 (COX-2) enhances the renocortical expression of pathogenic αv integrins. Aims: To study whether this effect is mediated by prostaglandin E2 (PGE2) acting through its EP3 receptor in cultured rat mesangial cells (MCs). Methods: MCs were incubated with lipopolysaccharide (LPS), celecoxib, PGE2, or the selective EP3 agonist, MB28767. The expression of COX-2, EP3, and αv integrin mRNA was measured by reverse transcriptase polymerase chain reaction. Results: LPS upregulated COX-2 expression 2.8-fold and αv integrin expression twofold. The COX-2 inhibitor celecoxib increased αv integrin mRNA expression twofold. Both exogenous PGE2 and the specific EP3 receptor agonist, MB28767, reduced constitutive αv integrin mRNA expression to half normal values. COX-2 dependent PGE2 suppressed the expression of αv integrin mRNA mediated by the EP3 receptor in MCs. Conclusions: These results suggest that COX-2 suppresses the expression of αv integrins by an increased production of PGE2 activating its EP3 receptor in glomerulonephritis.