The anti-inflammatory effects of vitamin D in mammary epithelial cells through sCD14 (P1329)

Abstract

Many studies have shown vitamin D to regulate immune cell responses, yet few have investigated whether vitamin D alters the immune responses of epithelial cells in barrier tissues, such as the mammary gland, to alter immune signaling within tissue microenvironments. Microarray screening and qPCR of human mammary epithelial cells treated with 1α,25-dihydroxyvitamin D (the active form of vitamin D) identified CD14 as a 1,25D induced gene. To follow up these findings, we examined whether 1,25D induced the expression of membrane CD14 or soluble CD14 and found that 1,25D increased the accumulation of sCD14 in a dose- and time- dependent manner but did not alter mCD14. To determine the effects of 1,25D-induced sCD14 from HME cells on Toll-like receptor 4 activation and cytokine secretion from monocyte-derived macrophages, we incubated HEK-Blue TLR4 reporter cells and differentiated THP1 macrophages in conditioned media from 1,25D-treated HME cells ± purified E.coli lipopolysaccharide. We found that conditioned media from 1,25D-treated cells had no significant effects on TLR4 activation in HEK Blue cells yet did promote the secretion of IL-10 from differentiated THP-1 macrophages in the presence of E.coli lipopolysaccharide. These results are the first to demonstrate vitamin D’s effects on the expression and secretion of CD14 in mammary epithelial cells and support the hypothesis that vitamin D promotes an anti-inflammatory environment via secretion of sCD14 in mammary tissue.