Further emergent evidence for the vitamin D endocrine system involvement in autoimmune rheumatic disease risk and prognosis

摘要: Recently, vitamin D has received increased worldwide attention for its involvement in reducing risk several chronic diseases including many cancers, infectious diseases, type 1 diabetes and notably autoimmune rheumatic diseases.1 The final active metabolite of (1,25(OH)D3) is considered a steroid hormone origin from cholesterol (D-hormone), like glucocorticoids exerts immunomodulatory activities (figure 1).2 ,3 Figure 1 Newly identified target genes calcitriol (D hormone) reveal multiple molecular pathways anti-inflammatory actions 1,25(OH)D3 cell types. These include: inhibition prostaglandin (PG) synthesis biological actions; p38 stress kinase activation production proinflammatory cytokines such as IL-6 (via induction MAP phosphatase 5 (MKP5 expression); nuclear factor κB (NF-κB) signalling which results the attenuation interleukin-8 (IL-8) up-regulation expression insulin-like growth binding protein-3 (IGFBP-3); angiogenesis due to suppressive effects on proangiogenic factors hypoxia-inducible (HIF-1) vascular endothelial factor; increase E-cadherin, leading invasion metastasis. Solid lines indicate direct calcitriol, dotted downstream calcitriol. Pathophysiological investigations confirm that severe hypovitaminosis D, genetically predisposed subjects, can impair self tolerance immune responses by compromising regulation dendritic cells, regulatory T-lymphocytes (Tregs), Th1 cells B function.3 Cross-sectional studies have shown deficient serum levels (25(OH)D) (<20 ng/ml) are present significant percentage, not only patients with sclerosis (MS), diabetes, systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), but also healthy subjects.4 ,5 In addition, presence 25(OH)D deficiency (<10 ng/ml) …