Decreased nitric oxide and prostaglandin E2 production in response to VIP in the uterus during a Th1 response, in NOD mice.

ROCA V, LUCIANA LAROCCA, JULIETA AISEMBERG, ANA FRANCHI Y CLAUDIA PEREZ LEIROS

Rio de Janeiro

Congreso; 1er Congreso Iberoamericano de Neuroinmunomodulación; 2005

CIBANIM

The non obese diabetic (NOD) mouse is a model of spontaneous Th1 response against exocrine glands that provides a valuable tool to study the initiation and progression of both autoimmune response and secretory dysfunction resembling Sjögren’s syndrome. NOD mice present a decreased birthrate from the third parturition onward compared to other mice strains. During the peri-implantation period, the endometrium behaves as an active secretory gland. VIP is a common messenger of both nervous and immune systems mediating secretory and inflammatory responses promoting a Th2 profile. It has also been characterized as a regulation factor of fetal growth and embryonic development. Nitric oxide (NO) and prostaglandin E2 (PGE2) play key roles in ovulation, fecundation, embryonic transport, implantation, uterine quiescence and parturition. In previous works, we have shown a loss of NOS activity in exocrine glands and a lower secretion of amylase in response to VIP in NOD mice. OBJETIVES The aim of this work was to study the effect of VIP on the production of NO, PGE2 and cAMP in uterus and spleen cells of NOD mice. METHODS We measured NOS activity by the production of L-citrulline. cAMP accumulation and PGE2 production by RIA, and western blot with specific antibodies for NOS and COX isoforms. BALB/c mice were used as control. RESULTS Our results showed a decreased basal NOS activity and PGE production in NOD mice uterus compared to control BALB/c mice. This difference in activity was more evident in Proestrous and it was not due to a lower protein expression. VIP had no effect on NOS activity and PGE2 production in NOD mice uterus compared to normal BALB/c mice. Similarly, a lower response to VIP was seen in cAMP accumulation in NOD mice spleen cell culture. CONCLUSION At least two important mediators in successful pregnancy, NO and PGE2, are altered in NOD mice uterus in the course of a Th1 response against the exocrine glands. In this model, VIP failed to activate common signaling pathways of both uterus and splenocytes.   This work was funded by PICT 10901 (2004) from ANPCyT and PIP 2072 (2004) from CONICET.