Regulatory effects of 1,25-dihydroxyvitamin D3 on vascular smooth muscle cells.
Inflammatory response has been recognized as a central feature in the development and progression of atherosclerosis, and VSMCs (Vascular Smooth Muscle Cells) - the main cellular component of media, play an important role in this process. Many reports indicate that the biologically active vitamin D metabolite - 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) = calcitriol), besides its well established role in calcium homeostasis, plays an essential role in the regulation of the inflammation process. The aim of this study was to determine the regulatory effects of calcitriol, applied at two supra-physiological doses (10 nM and 100 nM), in VSMC culture. Secretion of the pro-inflammatory cytokines, IL-6 and TNF-α, was significantly attenuated in calcitriol-treated VSMC culture, but the level of anti-inflammatory TGF-β was generally unchanged. Since in advanced atherosclerosis lesions several cell types, including VSMCs, overproduce the HSP70 chaperone protein, we also checked the effects of calcitriol on its synthesis. The presence of 1,25(OH)(2)D(3) did not affect HSP70 synthesis under physiological conditions but the synthesis of HSP70 in VSMCs exposed to heat shock was significantly inhibited by calcitriol (=100 nM). We observed that 1,25(OH)(2)D(3) induced SOD 1 activity, stimulated the expression of IκB-α, and did not influence the level of NF-κB-p65 in VSMCs. The results of our study suggest that 1,25(OH)(2)D(3) may serve as a natural anti-inflammatory agent and may therefore play a beneficial role in the physiology of VSMC in some contexts of atherosclerosis.
Department of Plant Physiology and Biotechnology, University of Gdańsk, Poland. stefantukaj@gmail.com
Stefan
S
Tukaj
Piotr
P
Trzonkowski
Cecylia
C
Tukaj
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D017209:Apoptosis; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D019610:Cytoprotection; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D003470:Culture Media; D018840:HSP70 Heat-Shock Proteins; D020672:I-kappa B Proteins; D053582:Interleukin-1alpha; D015850:Interleukin-6; C000606206:Nfkbia protein, rat; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002117:Calcitriol