Indomethacin modulates BMMC migration through prostaglandin and/or PPARƳ after sciatic nerve injury

CASALI CI; USACH V; PIÑERO G; PARRA L; WEBER K; SOTO PA; FERNÁNDEZ TOMÉ MC; CLARA P. SETTON

Córdoba

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

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

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 and PGJ2 levels in control and injured nerves. Considering that PGJ2 is an endogenous modulator of PPARƳ, the aim of the present work was to evaluate whether indomethacin prevent the inflammation associated with injury through ciclooxigenase 1 or 2 (COX -1 or -2) activity or PPARƳ activation.To this end, adult Wistar rats submitted to sciatic nerve crush were treated with indomethacin and the expression 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 as control.The increase in IOD levels associated to COX-1 induced by the injury was blocked by indomethacin. COX-2 expression was detected only at the mRNA level from day 4 post injury. PPARƳ immunofluorescence distribution was modified by indomethacin.Our results suggest that indomethacin avoids BMMC migration not only through PG biosynthesis inhibition but also affecting the expression/localization of PPARƳ. Further experiments are necessary to confirm this dual effect of indomethacin.