Pivotal role of vitamin D in regulation of inflammatory diseases including cancer, diabetes and autoimmune disorders / Impact of individual disposition and biological variations

Vitamin D deficiency is found among one billion human throughout the word, which is associated with increased risk of number of diseases development, such as osteoporosis in adults, rickets in children , as well as various inflammatory disorders including various autoimmune diseases ( i.e., multiple scleorosis, IBD, diabetes type 1 ( TIDM), diabetes type 2 ( T2DM), ),and infectious , cardio vascular , and neurological diseases ,as well as various cancers ( i.e., prostate, breast , colon, gastric, lung, ovarian, skin, bladder, multiple myeloma ) . With special interest, application of proper vitamin D therapeutic strategy reveal an effective approach for preventive, as well therapeutic challenge for many established diseases linked to vitamin D deficiencies. For this therapeutic approach one is required understanding of specific individual biological and conditional status of the person prior to the initiation of the treat -ment. Genome-wide analyses have redefining the pivotal biological role of vit. D on more sixty different cell types of both arms of innate and adaptive immune system , as well as non-immune cell types. In this connection, one of the most active metabolite of vit D( 1, 25(OH)2D , calcitriol, which bind to vitamin D receptor(VDR) to target more than one thousand human genes to direct divers biological function to maintain homeostasis. For example, studies of hundreds of primary 1,25 ( OH) 2D target genes from immune cells clearly ,have demonstrate , that 1,25(OH)2 play crucial role in of induction of anti bacterial proteins in macrophages and dendritic cells (DC) , in modulation of antigen presenting cells, down regulation of T cell proliferation and phenotypic changes , with over-arching effects being to down-regulate immune cells involve in inflammation and promote immune tolerance . In this connection, further genome wide analyses have highlighted, that cytokines pathways can exert positive and negative influence on intracrine 25 vit D system to either enhance or abrogate response to calcitriol. Of further interest 1,25(OH)2D plays a critical role in recruitment and regulation of nuclear transcription factor VDR and retinoid –X receptor (RXR)complex to binds to vitamin D response element (VDRE) in the promoter region of the target genes to recruits transcriptional coactivators or co-repressors to regulate mRNA expression of the target genes.Collectively , vit. D goes through a series of complex biological pathways within each specific bio system to become function or non functional. An effective metabolism of the vit D is generally, govern by individual’s genetic predisposition of the individual , as well as extrinsic and intrinsic influences. For example , VDR polymorphism (i.e., Taq-I, Basm-I, APa-I, Fok-I, Hom-IR) have shown diverse effect on binding ,anti proliferative and anti inflammatory effect of 1,25(OH)2D3 . Furthermore, Interferon ¥ and interleukin-15 exert a positive effect on induction of CYP27B1 expression, whereas, IL-10 , IFN-Β, IL-4, CYP24A1, Fibroblast growth factor 23 ( FGF23) show a negative effect on induction CYP27B1,also miRNA21 suppress CYP27B1. Of interest, in progressive inflammatory diseases , such as cancer overexpress CYP24A1 to become non- responsive to vit D.