Wöbke Thea K, Sorg Bernd L, Steinhilber Dieter
Institute of Pharmaceutical Chemistry, Goethe University Frankfurt Frankfurt, Germany.
Front Physiol. 2014 Jul 2;5:244. doi: 10.3389/fphys.2014.00244. eCollection 2014.
Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq.
血清维生素D水平的变化与炎症性疾病有关,如炎症性肠病(IBD)、类风湿性关节炎、系统性红斑狼疮、多发性硬化症(MS)、动脉粥样硬化或哮喘。全基因组和转录组研究表明,维生素D信号在多个层面调节许多炎症反应。这包括:(i)调节产生促炎介质的基因的表达,如环氧化酶或5-脂氧合酶;(ii)干扰转录因子,如调节炎症基因表达的核因子κB;以及(iii)激活信号级联反应,如介导炎症反应的丝裂原活化蛋白激酶。维生素D作用于多种组织和细胞类型,其中许多属于免疫系统,如单核细胞/巨噬细胞、树突状细胞(DCs)以及B细胞和T细胞,导致每种细胞类型产生各自的反应。这些特定维生素D效应的一个标志是参与炎症过程调节的基因的细胞类型特异性调节,以及维生素D信号与其他参与炎症的信号级联之间的相互作用。在不久的将来,一项重要任务将是通过使用染色质免疫沉淀(ChIP)、ChIP-seq和FAIRE-seq等技术,在分子水平上阐明维生素D调节炎症反应所涉及的调控机制。