INVESTIGADORES
LAROCCA Luciana
congresos y reuniones científicas
Título:
Decreased nitric oxide and prostaglandin E2 production in response to VIP in the uterus during a Th1 response, in NOD mice.
Autor/es:
ROCA V, LUCIANA LAROCCA, JULIETA AISEMBERG, ANA FRANCHI Y CLAUDIA PEREZ LEIROS
Lugar:
Rio de Janeiro
Reunión:
Congreso; 1er Congreso Iberoamericano de Neuroinmunomodulación; 2005
Institución organizadora:
CIBANIM
Resumen:
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
Sjögrens 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.