title: Vitamin D receptor protein is associated with interleukin-6 in human skeletal muscle.
abstract: Vitamin D is associated with skeletal muscle physiology and function and may play a role in intramuscular inflammation, possibly via the vitamin D receptor (VDR). We conducted two studies to examine (1) whether serum 25-hydroxyvitamin D (25OHD) and/or intramuscular VDR protein concentrations are associated with intramuscular interleukin-6 (IL-6) and/or tumor necrosis factor-α (TNFα); and (2) whether 16-week supplementation with vitamin D3 alters intramuscular IL-6 and/or TNFα. Potential-related signaling pathways were also examined. Muscle biopsies of 30 older, mobility-limited adults were obtained at baseline. A subset of 12 women were supplemented with either 4,000 IU/day of vitamin D3 (N = 5) or placebo (N = 7), and biopsies were repeated at 16 weeks. Serum 25OHD was measured, and intramuscular VDR, IL-6, and TNFα gene expressions and protein concentrations were analyzed. Baseline serum 25OHD was not associated with intramuscular IL-6 or TNFα gene expression or protein concentration. Baseline intramuscular VDR protein concentration, adjusted for baseline serum 25OHD, was positively associated with intramuscular IL-6 gene expression (n = 28; p = 0.04), but negatively associated with intramuscular IL-6 protein (n = 18; p = 0.03). Neither intramuscular IL-6 nor TNFα gene expression was different between placebo (n = 7) or vitamin D3 supplementation groups (n = 5) after 16 weeks (p = 0.57, p = 0.11, respectively). These data suggest that VDR is a better predictor than serum 25OHD concentration of intramuscular IL-6 gene and protein expressions. A similar relationship was not observed for TNFα expression. Further, supplementation with 4,000 IU vitamin D3 per day does not appear to affect intramuscular IL-6 or TNFα gene expression after 16 weeks.
authors.affiliation: Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA, 02111, USA, rachele.pojednic@joslin.harvard.edu.
authors.forename: Rachele M
authors.initials: RM
authors.lastname: Pojednic
authors.forename: Lisa
authors.initials: L
authors.lastname: Ceglia
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
authors.forename: Bess
authors.initials: B
authors.lastname: Dawson-Hughes
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D018167:Receptors, Calcitriol; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C579457:VDR protein, human; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D