THE ROLE OF CERVICAL ENDOCANNABINOID SYSTEM IN THE MODULATION OFLIPOPOLYSACCHARIDE-INDUCED PROINFLAMMATORY RESPONSE

MARVALDI, CAROLINA; HERRERO LO GUIDICE, FELISA MARIA; SCHANDER, JULIETA AYLEN; AISEMBERG, JULIETA; FRANCHI, ANA MARIA; WOLFSON, MANUEL LUIS

CABA

Congreso; IFPA 2019- VIII SLIMP; 2019

Objectives:Previously, we demonstrated the presence of the endo-cannabinoid system (ECs) in murine cervix. Based on this, the objective ofthe present study was to investigate the mechanisms involved in theproinflammatory response in 15 day-pregnant mice cervix to lipopoly-saccharide (LPS) and its possible modulation through the ECs.Methods:The cervix is a critical organ for pregnancy maintenance . Dy-namic alterations in the structure of the cervical extracellular matrix driveflexibility and mechanical strength of the cervix throughout pregnancy,labor, and postpartum. Metalloproteases (MMPs) and cyclooxygenase 2(COX-2) are involved on events associated with labor induction like cervixripening.We performed an ex vivo model to evaluate MMPs activity and COX-2protein levels. Briefly, cervix from 15 day pregnant mice were obtained andcultured in presence or absence of LPS (1mg/ml) for 6 hours. Besides, weused specific cannabinoid receptors (CBs) antagonist AM251 (for CB1, 10-8M) and AM630 (for CB2, 10-8M). MMPs gelatinase activity was evaluatedby zymography and COX-2 protein levels by Western Blot.Results:We found that LPS increased significantly MMP9 and MMP2gelatinase activity in cervix (P<0.05) and this effect on MMP9 activity waspartially reverted by CB antagonists (AM251 or AM630) (p<0.05). On theother hand, we observed a significant increase in COX-2 protein level whencervix explants were cultured with LPS during 6 hours, when compared tocontrol. This increase was reverted by the presence of CB1 (AM251) andCB2 (AM630) antagonist, suggesting a role of those receptors in inflam-matory response.Conclusion:Collectively, these results suggested that the ECs is involved incervical remodeling induced by LPS, acting through CB1 and CB2 receptors.