Host defence mainly involves the action of the innate immune system via neutrophils and lymphocytes. The role of the vitamin D receptor (VDR) in the antimicrobial activity www.selleckchem.com/products/OSI-906.html against some bacteria has been reported. 1,25(OH)2D3 signals through the vitamin

D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. 1,25(OH)2D3 is a direct regulator of antimicrobial innate immune responses, upregulation and activation of VDR [2, 3]. VDR is a member of the nuclear receptor family [4]; it is tightly associated with its heterodimeric partner, RXR, and only this liganded VDR-RXR heterodimer can penetrate the deep groove of DNA molecules and recognize vitamin D responsive elements (VDREs) in the DNA sequence of vitamin D-regulated genes [5]. The VDR/RXR complex controls more than 900 genes involved in a wide array of physiologic functions including calcium homeostasis, growth control, differentiation and apoptosis of many cell types, regulation of immune responses and cytokine production [6, 7]. Moreover, vitamin D deficiency Small molecule library chemical structure is adversely associated with autoimmune diseases and inflammation [8]. The target genes of the

VDR signal pathway include those of the enzyme Cyp24 and antimicrobial peptides (AMPs) β-defensin and cathelicidin (CAMP, also known as Pyruvate dehydrogenase LL37, CAP18 or FALL39). Diverse combinations of cationic AMPs, including α- and β-defensins and cathelicidins, form a major component of the innate immune system in mammals [9, 10]. Because bacteria have difficulty

developing resistance against AMPs and are quickly killed in the presence of AMPs, this class of antimicrobial agents is being commercially developed as a source of peptide antibiotics [11-13]. The CAMP gene is directly regulated by binding of the VDR to a VDRE located in its promoter region, and its expression has been shown to be upregulated by VDR signaling in multiple cell types, including epithelial cells [14]. CAMP plays a role in several important activities including bactericidal action, antiseptic action, chemoattraction, and promotion of angiogenesis and wound healing [14]. H. pylori infection leads to upregulation of the production of CAMP via the gastric epithelium; this could mean that CAMP contributes to regulating the balance between host mucosal defence and H. pylori survival mechanisms that govern chronic infection with this gastric pathogen [9, 10, 15]. Previous studies have shown that the vitamin D agonist 1α,25(OH)2D3 induces AMP gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines and that 1α,25(OH)2D3 along with LPS synergistically induces CAMP expression in neutrophils [2, 16].