Background: In experimental glomerulonephritis, inhibition of cyclooxygenase 2 (COX-2) enhances the renocortical expression of pathogenic alpha(v) integrins.
Aims: To study whether this effect is mediated by prostaglandin E(2) (PGE(2)) acting through its EP(3) receptor in cultured rat mesangial cells (MCs).
Methods: MCs were incubated with lipopolysaccharide (LPS), celecoxib, PGE(2), or the selective EP(3) agonist, MB28767. The expression of COX-2, EP(3), and alpha(v) integrin mRNA was measured by reverse transcriptase polymerase chain reaction.
Results: LPS upregulated COX-2 expression 2.8-fold and alpha(v) integrin expression twofold. The COX-2 inhibitor celecoxib increased alpha(v) integrin mRNA expression twofold. Both exogenous PGE(2) and the specific EP(3) receptor agonist, MB28767, reduced constitutive alpha(v) integrin mRNA expression to half normal values. COX-2 dependent PGE(2) suppressed the expression of alpha(v) integrin mRNA mediated by the EP(3) receptor in MCs.
Conclusions: These results suggest that COX-2 suppresses the expression of alpha(v) integrins by an increased production of PGE(2) activating its EP(3) receptor in glomerulonephritis.