Immunomodulators in Human Trophoblast-Uterus Cross Talk: Cytokines, growth factors and nitric oxide

Abstract

Successful reproductive outcome requires fine interplay of genetically dissimilar feto-placental unit, uterus and the local immune system. The role of immunomodulators elaborated by all the three has become increasingly apparent in the materno-fetal cross talk. Several of them, initially thought to be involved in pure immunological function, now seem to be of prime importance as determinants of optimal placental growth and function. These factors include growth factors, inflammatory and proinflammatry cytokines. Another molecule, nitric oxide, also involved in inflammatory responses, elaborated by macrophages and vascular endothelial cells, is now known to be synthesised by uterus and might have role in materno-fetal cross talk. To address the role of these cytokines and nitric oxide (NO) on optimal placental growth and function, we have studied their effect on trophoblast proliferation. Primary trophoblast cells, isolated from human term placentae and JEG-3 cells—a human trophoblast derived choriocarcinoma cell line, were used as in vitro models to assess the modulatory roles of cytokines and NO by metabolic labelling assay (MTT), Ki67 expression and BrdU incorporation. The results indicate that all the cytokines studied induced significant proliferation of trophoblast cells. Interestingly, maximum proliferation was obtained with inflammatory cytokines IL-1a, IL-6 and TNF-a and NO donors. A mechanism of cytokine and NO induced trophoblast proliferation is being hypothesised.