well this is interesting - to a really geeky mind like mine anyway - vit D3 and dexamethasone combo to modulate the inflammatory cytokines mentioned in the earlier links I posted that are related to psoriasis...Wonder if they did isomer work with Dex?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193760/
We postulated that a combination of immunosuppressive drugs, 1,25(OH) 2 -vitamin D3 (VitD3) and Dexamethasone (Dex), known to inhibit key transcription factors involved in the regulation of a number of inflammatory cytokines genes, would allow the development of a homogeneous population of IL-10–producing cells. VitD3 inhibits Th1-mediated autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis ( 24 , 25 ), and is currently used topically to treat psoriasis in humans ( 26 ). VitD3 affects APCs as well as lymphocytes and inhibits the production of a wide variety of pro-inflammatory and subsequent Th1 responses ( 26 – 28 ). Glucocorticoids (GCs), including Dex, are among the most potent immunosuppressive and antiinflammatory drugs currently available and are efficacious in the treatment of both Th1- and Th2-associated inflammatory diseases including rheumatoid arthritis and asthma ( 29 , 30 ). GCs inhibit both T cells and APCs at the level of proliferation and cytokine production ( 31 – 33 ). Recently, it has been shown that Dex enhanced IL-10 and reduced IL-4, IL-5, and IL-13 production in human CD4 + and CD8 + T cells ( 34 ). In addition, myelin basic protein (MBP)-specific Th2 cell lines generated in vitro in the presence of Dex plus IL-4 were shown to protect rats from EAE, although these cells lines would have undoubtedly contained Th2 cells ( 35 ).
Most importantly, VitD3 and Dex are known to inhibit the activation and action of important transcription factors involved in cytokine gene regulation, such as nuclear factor of activated T cells (NFAT), activator protein (AP)-1, and nuclear factor (NF)-?B ( 30 , 36 – 38 ). The repression of IL-2 gene transcription by VitD3 occurs via the vitamin D receptor (VDR)-dependent inhibition of NFAT and AP-1 complex formation ( 39 ). It has also been described that VitD3 mediates downregulation of NF-?B p50 and c-Rel protein expression in T cells ( 38 ). Glucocorticoids have been shown to interfere with the function of transcription factors such as AP-1 and NF-?B via protein–protein interactions ( 30 , 36 ), and in addition to inhibit IL-4 and possibly IL-2 gene expression by interfering with NFAT-dependent transactivation ( 37 ).
Here, we describe a novel strategy to induce the development of IL-10–producing regulatory T cells, using a combination of the immunosuppressive drugs VitD3 and Dex, which are known to impair cytokine gene regulation. In addition, we define factors that positively and negatively regulate their development, and provide novel findings regarding the possible molecular mechanisms for the physiological development of these IL-10–producing regulatory T cells.
