Abstract

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

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

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