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Vdr cathelicidin tuberculosis

Min Wan, Xiao Tang, Rokeya Sultana Rekha, S S V Jagadeeswara Rao Muvva, Susanna Brighenti, Birgitta Agerberth, Jesper Z Haeggström
Prostaglandin (PG)E2 is an arachidonic acid-derived lipid mediator that plays an important role in inflammation and immunity. In this study, we demonstrate that PGE2 suppresses basal and 1,25-dihydroxy vitamin D3 (VD3 )-induced expression of hCAP18/LL-37 via E prostanoid (EP)2 and EP4 receptors. In humans, VD3 up-regulates vitamin D receptor (VDR) expression and promotes transcription of the cathelicidin hCAP18/LL-37 gene, whereas PGE2 counteracts this effect. We find that PGE2 induces the cAMP/PKA-signaling pathway and enhances the expression of the inhibitory transcription factor cAMP-responsive modulator/inducible cAMP early repressor, which prevents VDR expression and induction of hCAP18/LL-37 in human macrophages...
May 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Matthew J Magee, Yan V Sun, James C M Brust, N Sarita Shah, Yuming Ning, Salim Allana, Angela Campbell, Qin Hui, Koleka Mlisana, Pravi Moodley, Neel R Gandhi
BACKGROUND: Vitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established...
2017: PloS One
Siswanto Siswanto, Lilik Zuhriyah, Kusworini Handono, Loeki Enggar Fitri, Sumarno Reto Prawiro
BACKGROUND: The innate immune response to tuberculosis infection may involve the increased production of nitric oxide and cathelicidin due to the up-regulated expression of the vitamin D receptor (VDR), though this proposed mechanism remains controversial. The aim of this study was to determine how the exposure of human monocytes to Mycobacterium tuberculosis (M. tuberculosis) DNA affects the production of nitric oxide and cathelicidin, as well as the expression of VDR. METHODS: This study was performed using monocytes obtained from healthy donors...
May 2015: Malaysian Journal of Medical Sciences: MJMS
Paramasivam Selvaraj, Murugesan Harishankar, Kolloli Afsal
Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages...
May 2015: Canadian Journal of Physiology and Pharmacology
Georgiana M Klug-Micu, Steffen Stenger, Andrea Sommer, Philip T Liu, Stephan R Krutzik, Robert L Modlin, Mario Fabri
The ability of T cells to activate antimicrobial pathways in infected macrophages is essential to host defence against many intracellular pathogens. Here, we compared the ability of two T-cell-mediated mechanisms to trigger antimicrobial responses against Mycobacterium tuberculosis in humans, CD40 activation and the release of interferon-γ (IFN-γ). Given that IFN-γ activates a vitamin D-dependent antimicrobial response, we focused on induction of the key components of this pathway. We show that activation of human monocytes via CD40 ligand (CD40L) and IFN-γ, alone, and in combination, induces the CYP27b1-hydroxylase, responsible for the conversion of 25-hydroxyvitamin D (25D) to the bioactive 1,25-dihydroxyvitamin D (1,25D), and the vitamin D receptor (VDR)...
May 2013: Immunology
P Selvaraj
Vitamin D plays a major role in bone mineral density and calcium homeostasis. Apart from its classical action, the active form of vitamin D [1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))] influences the innate and adaptive immune functions through vitamin D receptor (VDR) that are present in various cells of the immune system. Vitamin D deficiencies have been associated with development of tuberculosis (TB) disease, caused by Mycobacterium tuberculosis. Vitamin D(3) is shown to enhance macrophage phagocytosis of M...
2011: Vitamins and Hormones
Philip T Liu, Mirjam Schenk, Valencia P Walker, Paul W Dempsey, Melissa Kanchanapoomi, Matthew Wheelwright, Aria Vazirnia, Xiaoran Zhang, Andreas Steinmeyer, Ulrich Zügel, Bruce W Hollis, Genhong Cheng, Robert L Modlin
Antimicrobial effector mechanisms are central to the function of the innate immune response in host defense against microbial pathogens. In humans, activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. Here, we report that TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1beta and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1beta activity, involving the upregulation of both IL-1beta and IL-1 receptor, and downregulation of the IL-1 receptor antagonist...
June 5, 2009: PloS One
P Selvaraj, S Prabhu Anand, M Harishankar, K Alagarasu
INTRODUCTION: Vitamin D(3), which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations between low serum vitamin D(3) levels and increased risk of tuberculosis have been reported. STUDY SUBJECTS AND METHODS: Plasma 1,25 dihydroxy vitamin D(3) levels (1,25(OH)(2) D(3)) and ex vivo levels of VDR protein from peripheral blood mononuclear cells were studied in 65 pulmonary tuberculosis (PTB) patients and 60 normal healthy subjects (NHS) using enzyme-linked immunosorbent assay-based methods...
July 2009: Journal of Clinical Immunology
Stephan R Krutzik, Martin Hewison, Philip T Liu, Juan Antonio Robles, Steffen Stenger, John S Adams, Robert L Modlin
An essential function of the innate immune system is to directly trigger antimicrobial mechanisms to defend against invading pathogens. In humans, one such pathway involves activation by TLR2/1L leading to the vitamin D-dependent induction of antimicrobial peptides. In this study, we found that TLR2/1-induced IL-15 was required for induction of CYP27b1, the VDR and the downstream antimicrobial peptide cathelicidin. Although both IL-15 and IL-4 triggered macrophage differentiation, only IL-15 was sufficient by itself to induce CYP27b1 and subsequent bioconversion of 25-hydroxyvitamin D3 (25D3) into bioactive 1,25D3, leading to VDR activation and induction of cathelicidin...
November 15, 2008: Journal of Immunology: Official Journal of the American Association of Immunologists
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