COX-2 dependent PGE2 downregulates αv integrin expression via the EP3 receptor in cultured mesangial cells
- 1Nephrologie und allgemeine Innere Medizin, Städtisches Klinikum Solingen, Gotenstraße 1, D-42653 Solingen, Germany
- 2Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum, D-40225 Düsseldorf, Germany
- Correspondence to: Professor P Heering Department of Medicine III, Solingen General Hospital, University of Cologne, Gotenstraße 1, D-42653 Solingen, Germany; heeringklinikumsolingen.de
- Accepted 16 October 2003
Abstract
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.
- COX-2, cyclooxygenase 2
- LPS, lipopolysaccharide
- MC, mesangial cell
- PGE2, prostaglandin E2
- RT-PCR, reverse transcriptase polymerase chain reaction
