title: Vitamin D elicits anti-inflammatory response, inhibits contractile-associated proteins, and modulates Toll-like receptors in human myometrial cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Women's Health Research, Meharry Medical College, Nashville, TN 37208, USA. cthota@mmc.edu
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Thota
authors.forename: Takeisha
authors.initials: T
authors.lastname: Farmer
authors.forename: Robert E
authors.initials: RE
authors.lastname: Garfield
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D005260:Female; D006801:Humans; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003285:Contractile Proteins; D051193:Toll-Like Receptors; D014807:Vitamin D