Among the many functions of trophoblast cells is the production of prostaglandins (PGs); these signalling molecules regulate several fetoplacental vascular functions during gestation and trigger the events leading to parturition. PG production by trophoblast is modulated by many factors among which hormones and pro-inflammatory cytokine as well as by adverse conditions, such as hypoxia. The present research was undertaken to verify if HTR-8/SVneo cells, derived from the human trophoblast at the first trimester of pregnancy, are able to synthesize PGE2 and behave as a target for this prostanoid. Our results demonstrate that these cells produce very low amounts of PGE2 in basal conditions; under interleukin-1 beta stimulation, the release of the prostanoid becomes statistically significant only after 24 h, a pattern that is quite different from that found in other intrauterine tissues, such as amnion. HTR-8/SVneo cells respond to PGE2 with a dramatic increase of the intracellular cyclic adenosine 3’,5’-monophosphate (cAMP) levels, that are synergistically elevated when the adenylyl cyclase is activated by forskolin. This response is presumable mediated by EP2 and EP4 receptors since our RT-PCR experiments reveal the presence of mRNA only for these two receptor subtrypes, but not for EP1 and EP3 receptors. In the light of known influence of prostanoid on differentiation, proliferation and apoptosis in several cell types, it can be hypothesized that PGE2, interacting with EP2 and EP4 receptors, regulates these functions in human trophoblast at the first trimester of pregnancy.
HTR-8/SVneo cells as a target for prostaglandin E2 action: involvement of EP2 and EP4 receptors
PAVAN, Barbara;VESCE, Fortunato;BIONDI, Carla
2003
Abstract
Among the many functions of trophoblast cells is the production of prostaglandins (PGs); these signalling molecules regulate several fetoplacental vascular functions during gestation and trigger the events leading to parturition. PG production by trophoblast is modulated by many factors among which hormones and pro-inflammatory cytokine as well as by adverse conditions, such as hypoxia. The present research was undertaken to verify if HTR-8/SVneo cells, derived from the human trophoblast at the first trimester of pregnancy, are able to synthesize PGE2 and behave as a target for this prostanoid. Our results demonstrate that these cells produce very low amounts of PGE2 in basal conditions; under interleukin-1 beta stimulation, the release of the prostanoid becomes statistically significant only after 24 h, a pattern that is quite different from that found in other intrauterine tissues, such as amnion. HTR-8/SVneo cells respond to PGE2 with a dramatic increase of the intracellular cyclic adenosine 3’,5’-monophosphate (cAMP) levels, that are synergistically elevated when the adenylyl cyclase is activated by forskolin. This response is presumable mediated by EP2 and EP4 receptors since our RT-PCR experiments reveal the presence of mRNA only for these two receptor subtrypes, but not for EP1 and EP3 receptors. In the light of known influence of prostanoid on differentiation, proliferation and apoptosis in several cell types, it can be hypothesized that PGE2, interacting with EP2 and EP4 receptors, regulates these functions in human trophoblast at the first trimester of pregnancy.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.