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Vitamin D Attenuates TNFα‐induced Chemokine Production in Developing Human Airway Smooth Muscle Cells
Author(s) -
Britt Rodney,
Faksh Arij,
Vogel Elizabeth,
Thompson Michael,
Pandya Hitesh,
Amrani Yassine,
Pabelick Christina,
Prakash YS
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1030.2
Subject(s) - calcitriol , ccl5 , calcitriol receptor , chemokine , tumor necrosis factor alpha , vitamin d and neurology , cytokine , medicine , ccl11 , endocrinology , inflammation , cancer research , chemistry , immunology , t cell , eotaxin , immune system , il 2 receptor
Children with low Vitamin D levels are at increased risk of developing asthma. In the present study, we tested the hypothesis that the Vitamin D receptor (VDR) agonist, calcitriol, will reduce tumor necrosis factor‐α (TNF‐α)‐induced expression of chemokines in human fetal airway smooth muscle cells (fASM). Methods and Results Human fASM cells were dissociated from canalicular stage (18‐22 weeks gestation) lung tissue (de‐identified samples, in vitro use only and considered exempt by Mayo Institutional Review Board). Fetal ASM cells were pre‐treated with vehicle (0.001% DMSO) or 100 nM calcitriol for 1 h, and then exposed to 10 ng/mL TNFα for 6 or 24 h. Expression of CCL5 and CCL11 were measured by quantitative real time PCR and ELISA. Cells were transfected with VDR siRNA. Treatment with TNFα for 6 h increased mRNA expression and secretion of CCL5 and CCL11. While pre‐treatment with calcitriol reduced CCL5 and CCL11 expression in the presence of TNFα. Knockdown of the VDR expression demonstrated that calcitriol's effects are mediated through VDR. Conclusions These novel data demonstrate that calcitriol modulates cytokine enhancement of chemokines in developing ASM. Vitamin D may be a new therapeutic target in reducing inflammation in the immature airway. Supported by NIH F32 HL123075 (Britt), T32 HL105355 (Vogel), and R01s HL088029 and HL056470 (Prakash), and the Mayo Clinic Department of Anesthesiology (Pabelick, Prakash).