Functional regulation of thymic stromal lymphopoietin on proliferation and invasion of trophoblasts in human first-trimester pregnancy

Abstract

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers the dendritic cell-mediated T(H)2 response and regulatory T cell expansion. The aim of this study is to evaluate whether TSLP and TSLP receptor (TSLPR) are expressed in primary human extravillous trophoblast (EVT), how proimflammatory cytokines (tumor necrosis factor (TNF)-alpha, IL-1beta), T(H)2 and T(H)3 cytokines (IL-4, TGF-beta) and pregnancy-associated hormones regulate TSLP production by EVT and whether the SLP-TSLPR interaction affects the biological behavior of trophoblsts. We assessed TSLP mRNA and protein expression by real-time RT-PCR, ELISA and immunochemistry, respectively. We further investigated effects of TSLP on the proliferation and invasion of trophoblast cells in vitro. The primary EVTs constitutively expressed TSLP and TSLPR. IL-4 and TNF-alpha or pregnancy-associated hormones result in a significant increase in TSLP mRNA expression and protein release from EVT, and TSLP promotes primary EVT proliferation and invasion in vitro. This study has demonstrated that the first-trimester human trophoblast cells express TSLP and TSLPR, that cytokine milieu which mimics the maternal-fetal interface modulates expression of TSLP in trophoblast and that TSLP stimulates trophoblast proliferation and invasion. This suggests that TSLP plays an important role in human EVT invasion and placentation in human early pregnancy.