SHORT REPORT

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

C Waldner¹, K Schrör² and P Heering¹

¹ Nephrologie und allgemeine Innere Medizin, Städtisches Klinikum Solingen, Gotenstraße 1, D-42653 Solingen, Germany
² Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum, D-40225 Düsseldorf, Germany

Correspondence to:
Correspondence to:
Professor P Heering
Department of Medicine III, Solingen General Hospital, University of Cologne, Gotenstraße 1, D-42653 Solingen, Germany; heering{at}klinikumsolingen.de

Background: In experimental glomerulonephritis, inhibition of cyclooxygenase 2 (COX-2) enhances the renocortical expression of pathogenic _v 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 _v integrin mRNA was measured by reverse transcriptase polymerase chain reaction.

Results: LPS upregulated COX-2 expression 2.8-fold and _v integrin expression twofold. The COX-2 inhibitor celecoxib increased _v integrin mRNA expression twofold. Both exogenous PGE₂ and the specific EP₃ receptor agonist, MB28767, reduced constitutive _v integrin mRNA expression to half normal values. COX-2 dependent PGE₂ suppressed the expression of _v integrin mRNA mediated by the EP₃ receptor in MCs.

Conclusions: These results suggest that COX-2 suppresses the expression of _v integrins by an increased production of PGE₂ activating its EP₃ receptor in glomerulonephritis.

Keywords: COX-2; v integrins; EP3 receptor; celecoxib

Abbreviations: COX-2, cyclooxygenase 2; LPS, lipopolysaccharide; MC, mesangial cell; PGE₂, prostaglandin E₂; RT-PCR, reverse transcriptase polymerase chain reaction

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