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home:pathogenesis:vitamind:metabolism [06.07.2017] – [Mechanisms by which bacteria affect levels of 25-D and 1,25-D] sallieqhome:pathogenesis:vitamind:metabolism [01.01.2019] – [Metabolism of vitamin D and the Vitamin D Receptor] sallieq
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 A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin-D (25-D) and that consuming greater quantities of vitamin D, which elevates 25-D levels, alleviates symptoms of disease. Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation, which is in line with the reports of symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies has given way to a more complex description of action. When active, the Vitamin D nuclear receptor (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides.  A number of studies have suggested that patients with chronic inflammatory diseases are deficient in 25-hydroxyvitamin-D (25-D) and that consuming greater quantities of vitamin D, which elevates 25-D levels, alleviates symptoms of disease. Some years ago, molecular biology identified 25-D as a secosteroid. Secosteroids would typically be expected to depress inflammation, which is in line with the reports of symptomatic improvement. The simplistic first-order mass-action model used to guide the early vitamin studies has given way to a more complex description of action. When active, the Vitamin D nuclear receptor (VDR) affects transcription of at least 913 genes and impacts processes ranging from calcium metabolism to expression of key antimicrobial peptides. 
  
-Located in the nucleus of a variety of cells including immune cells, the VDR is a control system of sorts. When exposed to infection and damage, especially that which is caused by pathogens, the body begins to convert the inactive form 25-D into the active form, 1,25-D. As cellular concentrations of 1,25-D increase, 1,25-D activates the VDR, turning on any number of genes the receptor transcribes. +Located in the nucleus of a variety of cells including immune cells, the VDR is a control system of sorts. When exposed to infection and damage, especially that which is caused by pathogens, the body begins to convert the inactive form 25-D into the active form, 1,25-D. As cellular concentrations of 1,25-D increase, 1,25-D activates the VDR, turning on any number of genes the receptor transcribes.  [[https://autoimmunityresearch.org/hormones.pdf|Hormonal changes result from change in 1,25 dihydroxyvitamin-D]]
  
 According to a 2010 analysis, the VDR significantly affects 229 human genes. Many of these genes have long been associated with autoimmune diseases and cancers including, for example, the genes IRF8 (linked to multiple sclerosis), and PTPN2 (connected to Crohn's disease and type I diabetes).(({{pubmed>long:20736230}})) The activation of certain genes also leads to the synthesis of antimicrobial peptides. The antimicrobial peptides are the body's "natural antibiotics" and have a potent anti-bacterial effect. According to a 2010 analysis, the VDR significantly affects 229 human genes. Many of these genes have long been associated with autoimmune diseases and cancers including, for example, the genes IRF8 (linked to multiple sclerosis), and PTPN2 (connected to Crohn's disease and type I diabetes).(({{pubmed>long:20736230}})) The activation of certain genes also leads to the synthesis of antimicrobial peptides. The antimicrobial peptides are the body's "natural antibiotics" and have a potent anti-bacterial effect.
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  <blockquote> In particular, the expression of 1α-OHase [1 α-hydroxylase] by activated macrophages and epidermal keratinocytes [skin cells] suggests a role for 1,25(OH)2D3 [1,25-D] as an immunomodulatory and/or antiproliferative hormone. </blockquote>   <blockquote> In particular, the expression of 1α-OHase [1 α-hydroxylase] by activated macrophages and epidermal keratinocytes [skin cells] suggests a role for 1,25(OH)2D3 [1,25-D] as an immunomodulatory and/or antiproliferative hormone. </blockquote> 
  
-  * **synovial fluid surrounding the joints of patients with rheumatoid arthritis** – Mawer //et al// found that 1,25-D levels were particulary elevated in the synovial fluid surrounding the joints of patients with rheumatoid arthritis (RA).(({{pubmed>long:1950677}})) In this study, median serum levels of 1,25-D at baseline was not elevated in the RA patients — only 24 pg/ml. Thus, the extrarenal synthesis of 1,25-D was not obvious from the routine blood test for 1,25-D. There is no reason to think that the metabolism of other diseases is any different. +  * **synovial fluid surrounding the joints of patients with rheumatoid arthritis** – Mawer //et al// found that 1,25-D levels were particularly elevated in the synovial fluid surrounding the joints of patients with rheumatoid arthritis (RA).(({{pubmed>long:1950677}})) In this study, median serum levels of 1,25-D at baseline was not elevated in the RA patients — only 24 pg/ml. Thus, the extrarenal synthesis of 1,25-D was not obvious from the routine blood test for 1,25-D. There is no reason to think that the metabolism of other diseases is any different. 
   * **immune cells including macrophages** – Research has also shown that 1,25-D is synthesized in cells of the immune system, including the T cells and antigen-presenting cells(({{pubmed>long:14696037}})) as well as the macrophages.(({{pubmed>long:11158062}})) (({{pubmed>long:12887108}})) The fact that the immune cells are a site for 1,25-D synthesis is notable, because it is these cell types, especially macrophages, which are often infected by the Th1 pathogens.    * **immune cells including macrophages** – Research has also shown that 1,25-D is synthesized in cells of the immune system, including the T cells and antigen-presenting cells(({{pubmed>long:14696037}})) as well as the macrophages.(({{pubmed>long:11158062}})) (({{pubmed>long:12887108}})) The fact that the immune cells are a site for 1,25-D synthesis is notable, because it is these cell types, especially macrophages, which are often infected by the Th1 pathogens. 
  
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 {{topic>tutorials papers +vitamin_D -CCR2b}} {{topic>tutorials papers +vitamin_D -CCR2b}}
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 +===== Read more research =====
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 +{{https://www.ncbi.nlm.nih.gov/pubmed/16902422|Wavelength-dependent induction of CYP24A1-mRNA after UVB-triggered calcitriol synthesis in cultured human keratinocytes.}}
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 +{{https://www.ncbi.nlm.nih.gov/pubmed/19146580|Role of the vitamin D3 pathway in healthy and diseased skin--facts, contradictions and hypotheses.}}
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 +{{tag>pathogenesis Science_behind_vitamin_D}}
 ===== Notes and comments ===== ===== Notes and comments =====
  
home/pathogenesis/vitamind/metabolism.txt · Last modified: 09.14.2022 by 127.0.0.1
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