IL-33 restricts invasion and adhesion of trophoblast cell line JEG3 by downregulation of integrin α4β1 and CD62L

Interleukin-33 (IL-33) promotes migration of cancer cells through downregulating the expression of E-cadherin. Previous studies have demonstrated that IL-33 stimulates the proliferation of trophoblasts. However, the effect of IL-33 on the adhesion and invasion of trophoblasts has not been investigated in detail. In the present study, the expression of IL-33 and its receptor, IL-1 receptor-like 1 (ST2), was examined in villi from women during early pregnancy using immunohistochemistry. ST2 expression on human trophoblast and choriocarcinoma cell lines JAR, BeWo, JEG3 and HTR8 was confirmed by flow cytometry (FCM) assay. The effect of recombinant human IL-33 (rhIL-33) on adhesion, invasion and associated molecules was analyzed by cell adhesion, Matrigel invasion and FCM assays. The current study identified that human trophoblasts expressed IL-33 and ST2. RhIL-33 inhibited trophoblast invasion and adhesion, and decreased adhesion and invasion-associated molecules such as integrin alpha 4 beta 1 and CD62L. Therefore, these results suggest that IL-33 may serve an important role in limiting invasion and implantation of trophoblasts by adhesion and invasion-associated molecules, contributing to the formation of the placenta and maintenance of normal pregnancy during early pregnancy.