Indomethacin effect on BMMC migration: Prostaglandin synthesis inhibition or PPARgamma; activation

CASALI, CECILIA IRENE; VANINA USACH; PIÑEIRO, GONZALO; PARRA LEANDRO; WEBER KAREN; SOTO PAULA ; FERNANDEZ TOME , MARIA DEL CARMEN; SETTON PATRICIA

CORDOBA

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

SAIB

Our group has demonstrated that indomethacin inhibited the migration of systemically transplanted bone marrow mononuclear cells(BMMC) to the lesion area, and promoted a decrease in prostaglandin E2 (PGE2) biosynthesis and a significant increase in PGD2 andPGJ2 levels in control and injured nerves. Considering that PGJ2 is an endogenous modulator of PPARƳ, the aim of the present workwas to evaluate whether indomethacin prevents the inflammation associated with injury through cyclooxygenase 1 or 2 (COX -1 or -2)activity or PPARƳ activation.To this end, adult Wistar rats subjected to sciatic nerve crush were treated with indomethacin and theexpression of Cox-1 and -2 and PPARƳ were evaluated, as well as the synthesis of PGs at different times previous and post crush,through qPCR, immunohistochemistry and PG radioconversion, respectively. Naïve animals treated with indomethacin were used ascontrols.The increase in IOD levels associated to COX-1 induced by the injury was blocked by indomethacin. COX-2 expression wasdetected only at the mRNA level from day 4 post injury. PPARƳ immunofluorescence distribution was modified by indomethacin.Ourresults suggest that indomethacin prevents BMMC migration not only through PG biosynthesis inhibition but also affecting theexpression/localization of PPARƳ. Further experiments are necessary to confirm this dual effect of indomethacin.