RETINOIDS REGULATE TIGHT JUNCTIONAL RESISTANCE OF CULTURED HUMAN CERVICAL CELLS

The objective of the study was to determine the effect of retinoids on paracellular resistance across the cervical epithelium and the mechan isms involved. The experimental model was cultures of human CaSki cell s on filters, which retain phenotypic characteristics of the endocervi cal epithelium. End points for paracellular resistance were measuremen ts of transepithelial electrical resistance and fluxes of pyranine (a trisulfonic acid that traverses the epithelium via the intercellular s pace). Paracellular resistance was significantly increased in cells gr own in retinoid-free medium; the effect could be blocked and reversed with all-trans-retinoic acid (tRA) and with agonists of RAR and RXR re ceptors but only partially with retinol. The effect of tRA was dose de pendent and saturable, with a 50% effective concentration of 0.8 nM. T he increases in paracellular resistance induced by vitamin A deficienc y required longer incubation in retinoid-free medium than decreases in resistance induced by retinoic acid. tRA had only a minimal effect on paracellular resistance in cells maintained in regular medium. Retino id-free medium increased and tRA decreased the relative cation mobilit y across CaSki cultures. Also the effects of tRA were nonadditive to t hose of cytochalasin D (which decreases tight junctional resistance) a nd additive to those of ionomycin (which decreases the resistance of t he lateral intercellular space), suggesting that tRA modulates tight j unctional resistance. It is concluded that vitamin A determines the de gree of paracellular resistance across cervical cells by a mechanism t hat involves modulation of tight junctional resistance.