Interleukin-6 Stimulates Cell Migration, Invasion and Integrin Expression in HTR-8/SVneo Cell Line

Abstract Interleukin-6 (IL-6) is present in human endometrium throughout menstrual cycle and in pregnancy. Trophoblast also expresses IL-6. IL-6R and its associated signal transducer gp130 were found in trophoblast as well. IL-6 is generally assumed to be relevant for trophoblast invasion. This study was undertaken to determine influence of endogenous and externally added IL-6 on invasion and migration of first trimester of pregnancy trophoblast in vitro . Integrins α5 β1 and α1 β1 have been shown to play an important role in trophoblast invasion and the effect of IL-6 on the expression of these integrin subunits was studied. We are showing that in both isolated first trimester of pregnancy cytotrophoblast (CTB) and HTR-8/SVneo cell line IL-6 and IL-6R are present. The effect on migration was studied using cell wounding and migration test on HTR-8/SVneo cells. Effect of IL-6 and function blocking anti-IL-6 antibody in Matrigel invasion tests was studied on both cell types. The effect of IL-6 on integrin subunit expression was determined by cell-based ELISA and Western blot on HTR-8/SVneo cells. The results obtained show that exogenous IL-6 has stimulatory effect on cell migration in HTR-8/SVneo and invasion by both cell types. Function blocking anti-IL-6 inhibited unstimulated invasion by isolated first trimester cytotrophoblast and both cell migration and invasion in unstimulated HTR-8/SVneo. Integrin α5 expression was stimulated by IL-6 to 134% ( p < 0.05), α1 to 135% ( p < 0.005), and β1 to 134% ( p < 0.001) of control in cell-based ELISA, but also in Western blot. The data obtained show for the first time sensitivity of extravillous trophoblast cell line HTR-8/SVneo to IL-6, in addition to isolated first trimester cytotrophoblast. We conclude that both exogenous and endogenous IL-6 stimulate trophoblast cell migration and invasion, which may be partly attributable to stimulation of expression of the studied integrin subunits.