Paracrine mediators of mouse uterine epithelial cell transepithelial resistance in culture

Epithelial cell integrity at mucosal surfaces provides an effective physical barrier against potential pathogens that threaten reproductive health. We have used polarized epithelial cells from adult mouse uteri to investigate the roles of TNFalpha and TGFbeta, which are produced by uterine epithelial and stromal cells, and hepatocyte growth factor (HGF), produced by uterine stromal cells, in regulating epithelial cell integrity measured as transepithelial electrical resistance (TER). Exposure of epithelial cells to TNFalpha, TGFbeta, and HGF have profound effects on TER that are different from their known actions on TER at other mucosal surfaces. When incubated with TNFalpha, TER increased in a dose-dependent manner. In contrast, when cells were incubated with TGFbeta, TER was markedly but reversibly suppressed. Interestingly, HGF, when placed in the basolateral compartment, increased TER. Based on these findings, we conclude that TNFalpha, TGFbeta and HGF may play regulatory roles in modulating epithelial cell tight junctions. These studies suggest that factors, such as hormone balance, pathogen exposure as well as pregnancy, which affect cytokine and growth factor secretion, influence epithelial cell barrier protection within the female reproductive tract.