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

Abstract

OBJECTIVE Infection triggers inflammation which 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 NFκB pathway proteins in human uterine myometrial smooth muscle (UtSM) cells cultured in an inflammatory environment. STUDY DESIGN Inflammatory environment was simulated for UtSM cells by co-culturing them with monocyte lineage (THP1) cells. We measured the expression of inflammatory markers, contractile-associated factors, steroid hormone receptors and NFκB pathway proteins in UtSM cells cultured with THP1 cells in the presence and absence of vitamin D by RT-PCR and western analysis. RESULTS Monocytes secreted MIP-1α, MIP-1 β, IL-1β, IL6, and TNFα into the conditioned medium. In UtSM cells co-cultured with THP1 cells there was a significant (p<0.05) increase in the expression of inflammatory markers IL-1β, IL6, IL13 and TNFα; the contractile associated factors connexin-43, cox-2 and prostaglandin F2α receptor; the estrogen receptor α and progesterone receptors A and B. Vitamin D treatment of co-cultures decreased (p<0.05) the expression of inflammatory markers and contractile associated factors in UtSM cells. Similarly vitamin D decreased estrogen receptor α and progesterone receptors A to B ratio in UtSM cells co-cultured with THP1 cells. In addition, vitamin D treatment significantly (p<0.05) decreased monocyte induced p-IκBα in cytosol, NFκB-p65 in the nucleus and increased IκBα 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 via NFκB pathway.

Modulation of the inflammatory response of bovine mammary epithelial cells by cholecalciferol (vitamin D) during Staphylococcus aureus internalization

“…Cholecalciferol has anti-inflammatory activity because it reduces the production of pro-inflammatory cytokines, such as TNF-a [11]. Also, the 1,25(OH) 2 D 3 reduces the production of IL-1b [37]. Accordingly, in all the treatments cholecalciferol inhibited the gene expression of these cytokines in bMEC.…”

Vitamin D heritability and effect of pregnancy status in Vervet monkeys (Chlorocebus aethiops sabaeus) under conditions of modest and high dietary supplementation

“…Several studies reported low vitamin D levels in pregnant women (Dawodu and Wagner 2012; Wagner et al, 2012); however, role of vitamin D in pregnancy outcomes is yet to be fully described. Some studies speculate that given the presence of vitamin D receptors in gestational tissues, there is biological plausibility for variation of vitamin D concentrations during pregnancy (Thota et al, 2014). Interestingly, in the present study, pregnancy status was associated with reduced vitamin D concentrations regardless of diet.…”

Why is Preterm Birth Stubbornly Higher in African-Americans?

“…Indeed, we have recently reported that vitamin D deficiency is associated with an increased risk of PTB in African-Americans and Caucasians [10]. Additionally, we have demonstrated that vitamin D elicits anti-inflammatory response, and decreases expression of contractile factors in human uterine smooth muscle cells [11]. Furthermore, specific vitamin D receptor polymorphism has been associated with increased risk of spontaneous idiopathic preterm birth [12].…”

“…Among obstetrical societies, ACOG has issued brief committee opinion in July 2011 stating that there is insufficient evidence to recommend vitamin D supplementation for prevention of preterm birth [14]. However, in light of accumulating compelling recent literature [11,13]. Since issuance of that committee opinion, we would encourage reconsideration of evaluating and possibly adapting the Endocrine Society policy (which is co-sponsored by The Institute of Medicine), which could likely have positive impact and may help reduced the persistently high PTB rate and associated high infant mortality rate in this population.…”