Vitamin D attenuates cytokine-induced remodeling in human fetal airway smooth muscle cells. 2015

Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
Departments of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.

Asthma in the pediatric population remains a significant contributor to morbidity and increasing healthcare costs. Vitamin D3 insufficiency and deficiency have been associated with development of asthma. Recent studies in models of adult airway diseases suggest that the bioactive Vitamin D3 metabolite, calcitriol (1,25-dihydroxyvitamin D3 ; 1,25(OH)2 D3 ), 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.

UI MeSH Term Description Entries
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D002117 Calcitriol The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. 1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D014808 Vitamin D Deficiency A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406) Deficiency, Vitamin D,Deficiencies, Vitamin D,Vitamin D Deficiencies
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D056151 Airway Remodeling The structural changes in the number, mass, size and/or composition of the airway tissues. Airway Remodelling,Asthmatic Airway Remodeling,Asthmatic Airway Remodelling,Asthmatic Airway Wall Remodeling,Asthmatic Airway Wall Remodelling,Small Airway Remodeling,Small Airway Remodelling,Airway Wall Remodelling,Airway Remodeling, Asthmatic,Airway Remodeling, Small,Airway Remodelings,Airway Remodelings, Asthmatic,Airway Remodelings, Small,Airway Remodelling, Asthmatic,Airway Remodelling, Small,Airway Remodellings,Airway Remodellings, Asthmatic,Airway Remodellings, Small,Airway Wall Remodellings,Asthmatic Airway Remodelings,Asthmatic Airway Remodellings,Remodeling, Airway,Remodeling, Asthmatic Airway,Remodeling, Small Airway,Remodelings, Airway,Remodelings, Asthmatic Airway,Remodelings, Small Airway,Remodelling, Airway,Remodelling, Airway Wall,Remodelling, Asthmatic Airway,Remodelling, Small Airway,Remodellings, Airway,Remodellings, Airway Wall,Remodellings, Asthmatic Airway,Remodellings, Small Airway,Small Airway Remodelings,Small Airway Remodellings,Wall Remodelling, Airway,Wall Remodellings, Airway

Related Publications

Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
March 2016, Annals of the American Thoracic Society,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
December 2011, Cytokine,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
May 2018, Respiratory physiology & neurobiology,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
April 1998, Pediatric research,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
September 2008, British journal of pharmacology,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
July 2019, American journal of respiratory cell and molecular biology,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
September 2003, Respiratory physiology & neurobiology,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
February 2016, Expert review of respiratory medicine,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
October 2017, Journal of cellular and molecular medicine,
Rodney D Britt, and Arij Faksh, and Elizabeth R Vogel, and Michael A Thompson, and Vivian Chu, and Hitesh C Pandya, and Yassine Amrani, and Richard J Martin, and Christina M Pabelick, and Y S Prakash
June 2012, Current opinion in pharmacology,
Copied contents to your clipboard!