title: Vitamin D regulates contractile profile in human uterine myometrial cells via NF-κB pathway.
abstract: OBJECTIVE
  Infection triggers inflammation that, 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 that were cultured in an inflammatory environment.
  
  
  METHODS
  Inflammatory environment was simulated for UtSM cells by coculturing 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 that were cultured with THP1 cells in the presence and absence of vitamin D by real time polymerase chain reaction and Western blot analysis.
  
  
  RESULTS
  Monocytes secreted monocyte inflammatory protein-1α and -1β, interleukin (IL)-1β and 6, and tumor necrosis factor-α into the conditioned medium. In the UtSM cells that had been cocultured with THP1 cells, there was a significant (P < .05) increase in the expression of inflammatory markers IL-1β, -6, and -13 and tumor necrosis factor-α; 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 cocultures decreased (P < .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 that were cocultured with THP1 cells. In addition, vitamin D treatment significantly (P < .05) decreased monocyte-induced p-IκBα in cytosol and NFκB-p65 in the nucleus and increased IκBα in cytosol in UtSM cells.
  
  
  CONCLUSIONS
  Our results suggest that vitamin D treatment decreases inflammation-induced cytokines and contractile-associated factors in the uterine myometrial smooth muscle cells through the NFκB pathway.
authors.affiliation: Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN. Electronic address: cthota@mmc.edu.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Thota
authors.affiliation: Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN.
authors.forename: Archana
authors.initials: A
authors.lastname: Laknaur
authors.affiliation: Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN.
authors.forename: Takeisha
authors.initials: T
authors.lastname: Farmer
authors.affiliation: Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN.
authors.forename: Gwinnett
authors.initials: G
authors.lastname: Ladson
authors.affiliation: Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN.
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
authors.affiliation: Magee Women's Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Nahed
authors.initials: N
authors.lastname: Ismail
mesh_terms: D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D018920:Coculture Techniques; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D009215:Myometrium / Q000166:cytology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D018031:Connexin 43; D016207:Cytokines; D047628:Estrogen Receptor alpha; C500216:GJA1 protein, human; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D011980:Receptors, Progesterone; D011982:Receptors, Prostaglandin; C101118:progesterone receptor A; C097314:progesterone receptor B; C034671:prostaglandin F2alpha receptor; D000072000:NF-KappaB Inhibitor alpha; D014807:Vitamin D; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: NFκB; contractile-associated factor; inflammatory marker; monocyte; myometrial cell