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Vitamin D Elicits Anti-Inflammatory Response, Inhibits Contractile-Associated Proteins, and Modulates Toll-Like Receptors in Human Myometrial Cells

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Abstract

Infection during pregnancy triggers inflammation, which can increase myometrial contractions and the risk of premature labor and delivery. In this study, we assessed the effects of vitamin D, an anti-inflammatory ligand on cytokines, chemokines, toll-like receptors, and contractile-associated proteins on immortalized human myometrial smooth muscle (UtSM) cells stimulated with lipopolysaccharide (LPS), a bacterial endotoxin, or interleukin (IL)-1β and measured Toll-like receptor (TLR)-10 expression in pregnant myometrial tissues. A superarray analysis revealed downregulation of the chemokines monocyte chemoattractant protein (MCP)-1, Chemokine (C-X-C motif) ligand (CXCL)-10, CXCL-11, and chemokine (C-X3-C motif) ligand (CX3CL)-1; the proinflammatory cytokines IL-13 and tumor necrosis factor (TNF)-α; the TLR-4 and -5 and triggering receptor expressed on myeloid cells (TREM)-2 and upregulation of the anti-inflammatory cytokine IL-10, as well as Toll interacting protein (TOLLIP) and TREM-1 in vitamin D-treated UtSM cells. In the presence of LPS, vitamin D caused dose-dependent decreases in the messenger RNA expression of MCP-1, IL-1β, IL-13, TNF-α, TLR-4, and TLR-5, the contractile-associated proteins connexin 43, the oxytocin receptor, and the prostaglandin receptor but caused increases in IL-10 and TLR-10 in UtSM cells. The TLR-10 expression was higher in human myometrial tissue obtained from women at term not in labor compared to labor. Vitamin D also attenuated IL-1β-induced MCP-1, IL-6, connexin 43, cyclooxygenase (COX)-2, and prostaglandin receptor expression. Western analysis showed that vitamin D decreased MCP-1, TLR-4, and connexin 43 in the presence of LPS and decreased connexin 43 in the presence of IL-1β. Our results suggest that vitamin D can potentially decrease infection-induced increases in cytokines and contractile-associated proteins in the myometrium.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Center for Women’s Health Research, Meharry Medical College, 1005 Dr DB Todd Jr Blvd, 37208, Nashville, TN, USA

    Chandrasekhar Thota PhD, Takeisha Farmer MS & Ayman Al-Hendy MD, PhD

  2. St Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    Robert E. Garfield PhD

  3. University of Texas Medical Branch Galveston, Galveston, TX, USA

    Ramkumar Menon PhD

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  1. Chandrasekhar Thota PhD
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  2. Takeisha Farmer MS
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  4. Ramkumar Menon PhD
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  5. Ayman Al-Hendy MD, PhD
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Correspondence to Chandrasekhar Thota PhD.

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Thota, C., Farmer, T., Garfield, R.E. et al. Vitamin D Elicits Anti-Inflammatory Response, Inhibits Contractile-Associated Proteins, and Modulates Toll-Like Receptors in Human Myometrial Cells. Reprod. Sci. 20, 463–475 (2013). https://doi.org/10.1177/1933719112459225

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