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Vitamin D Attenuates Cytokine‐Induced Remodeling in Human Fetal Airway Smooth Muscle Cells
Author(s) -
Britt Rodney D.,
Faksh Arij,
Vogel Elizabeth R.,
Thompson Michael A.,
Chu Vivian,
Pandya Hitesh C.,
Amrani Yassine,
Martin Richard J.,
Pabelick Christina M.,
Prakash Y. S.
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24814
Subject(s) - calcitriol , medicine , vitamin d and neurology , endocrinology , inflammation , cytokine , vitamin d deficiency , fetus , immunology , biology , pregnancy , genetics
Asthma in the pediatric population remains a significant contributor to morbidity and increasing healthcare costs. Vitamin D 3 insufficiency and deficiency have been associated with development of asthma. Recent studies in models of adult airway diseases suggest that the bioactive Vitamin D 3 metabolite, calcitriol (1,25‐dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ), modulates responses to inflammation; however, this concept has not been explored in developing airways in the context of pediatric asthma. We used human fetal airway smooth muscle (ASM) cells as a model of the early postnatal airway to explore how calcitriol modulates remodeling induced by pro‐inflammatory cytokines. Cells were pre‐treated with calcitriol and then exposed to TNFα or TGFβ for up to 72 h. Matrix metalloproteinase (MMP) activity, production of extracellular matrix (ECM), and cell proliferation were assessed. Calcitriol attenuated TNFα enhancement of MMP‐9 expression and activity. Additionally, calcitriol attenuated TNFα and TGFβ‐induced collagen III expression and deposition, and separately, inhibited proliferation of fetal ASM cells induced by either inflammatory mediator. Analysis of signaling pathways suggested that calcitriol effects in fetal ASM involve ERK signaling, but not other major inflammatory pathways. Overall, our data demonstrate that calcitriol can blunt multiple effects of TNFα and TGFβ in developing airway, and point to a potentially novel approach to alleviating structural changes in inflammatory airway diseases of childhood. J. Cell. Physiol. 230: 1189–1198, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company