Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway

OBJECTIVE: Infection triggers inflammation that, in turn, enhances the expression of contractile-associated factors in myometrium and increases the risk of preterm delivery. In this study, we assessed vitamin D regulation of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NF kappa B pathway proteins in human uterine myometrial smooth muscle (UtSM) cells that were cultured in an inflammatory environment. STUDY DESIGN: Inflammatory environment was simulated for UtSM cells by coculturing them with monocyte lineage (THP1) cells. We measured the expression of inflammatory markers, contractile-associated factors, steroid hormone receptors, and NF kappa B pathway proteins in UtSM cells that were cultured with THP1 cells in the presence and absence of vitamin D by real time polymerase chain reaction and Western blot analysis. RESULTS: Monocytes secreted monocyte inflammatory protein-1 alpha and-1 beta, interleukin (IL)-1 beta and 6, and tumor necrosis factor-alpha into the conditioned medium. In the UtSM cells that had been cocultured with THP1 cells, there was a significant (P < .05) increase in the expression of inflammatory markers IL-1 beta, -6, and -13 and tumor necrosis factor-alpha; the contractile-associated factors connexin-43, Cox-2, and prostaglandin F-2 alpha receptor; the estrogen receptor a, and progesterone receptors A and B. Vitamin D treatment of cocultures decreased (P < .05) the expression of inflammatory markers and contractile-associated factors in UtSM cells. Similarly, vitamin D decreased estrogen receptor a and progesterone receptors A-to-B ratio in UtSM cells that were cocultured with THP1 cells. In addition, vitamin D treatment significantly (P < .05) decreased monocyteinduced p-I kappa B alpha in cytosol and NF kappa B-p65 in the nucleus and increased I kappa B alpha in cytosol in UtSM cells. CONCLUSION: Our results suggest that vitamin D treatment decreases inflammation-induced cytokines and contractile-associated factors in the uterine myometrial smooth muscle cells through the NF kappa B pathway.