COX-2 dependent PGE(2) downregulates alpha(v) integrin expression via the EP(3) receptor in cultured mesangial cells.
BACKGROUND
In experimental glomerulonephritis, inhibition of cyclooxygenase 2 (COX-2) enhances the renocortical expression of pathogenic alpha(v) integrins.


OBJECTIVE
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.
Waldner
C
C
Nephrologie und allgemeine Innere Medizin, Städtisches Klinikum Solingen, Gotenstrasse 1, D-42653 Solingen, Germany.
Schrör
K
K
Heering
P
P
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype
D039564:Integrin alphaV; D007527:Isoenzymes; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone