Vitamin D3 controls TLR4- and TLR2-mediated inflammatory responses of endometrial cells

Background: There is a significant association between intrauterine infection-associated inflammatory responses and such pregnancy complications as abortion and preterm labor. Here, we aimed to investigate anti-inflammatory effects of 1,25 (OH)2 D3 on pro-inflammatory cytokines secretion and expression of TLR2, TLR4 and MyD88 in endometrial stromal cells (ESCs) and whole endometrial cells (WECs). Method: WECs were treated with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) and ESCs were treated with LPS. IL-6, IL8 and TNF-α were quantified using ELISA technique. TLR2, TLR4 and MyD88 expression were assessed by RT-qPCR. TLR4 expression at the protein level was studied by Western blot technique. Results: 1,25 (OH)2 D3 significantly reduced TNF-α production in LPS-activated ESCs and TNF-α and IL-6 production by LTA-stimulated WECs. In contrast, 1,25 (OH)2 D3 pre-treatment increased production of IL-8 by LPS- and LTA-stimulated endometrial cells. 1,25 (OH)2 D3 pre-treatment markedly reduced LPS-induced TLR-4 protein expression by ESCs. LPS treatment of ESCs significantly induced MyD88 gene expression. This effect was reversed when these cells were pre-treated with 1,25 (OH)2 D3 before stimulation with LPS. Conclusion: 1,25 (OH)2 D3 is an immunomodulatory molecule essential for maintenance of endometrial immune homeostasis through controlling potentially harmful inflammatory responses associated with female reproductive tract infections. Key words: Vitamin D3, Endometrium, Inflammation, Toll like receptors, Pro-inflammatory cytokines