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      PU.1 and Epigenetic Signals Modulate 1,25-Dihydroxyvitamin D 3 and C/EBPα Regulation of the Human Cathelicidin Antimicrobial Peptide Gene in Lung Epithelial Cells

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          Abstract

          LL-37, the only known human cathelicidin which is encoded by the human antimicrobial peptide (CAMP) gene, plays a critical role in protection against bacterial infection. We previously demonstrated that cathelicidin is induced by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) in human airway epithelial cells with a resultant increase in bactericidal activity. In this study we identify key factors that cooperate with 1,25(OH) 2D 3 in the regulation of CAMP. Our results show for the first time that PU.1, the myeloid transcription factor (which has also been identified in lung epithelial cells), cooperates with the vitamin D receptor and C/EBPα to enhance the induction of CAMP in lung epithelial cells. Our findings also indicate that enhancement of 1,25(OH) 2D 3 regulation of CAMP by histone deacetylase inhibitors involves cooperation between acetylation and chromatin remodeling through BRG1 (a component of the SWI/SNF complex). BRG1 can be an activator or repressor depending on BRG1 associated factors. PRMT5, a methlytransferase which interacts with BRG1, represses 1,25(OH) 2D 3 induced CAMP in part through dimethylation of H4R3. Our findings identify key mediators involved in the regulation of CAMP gene in lung epithelial cells and suggest new approaches for therapeutic manipulation of gene expression in order to increase the antibacterial capability of the airway.

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          Author and article information

          Journal
          0050222
          4586
          J Cell Physiol
          J. Cell. Physiol.
          Journal of cellular physiology
          0021-9541
          1097-4652
          25 October 2018
          01 November 2018
          July 2019
          25 October 2019
          : 234
          : 7
          : 10345-10359
          Affiliations
          [1 ]Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, the State University of New Jersey, New Jersey Medical School, Newark New Jersey 07103
          [2 ]Department of Internal Medicine, Ohio State University, Columbus Ohio 43210
          Author notes
          Correspondence: Dr. Sylvia Christakos, Dept. of Microbiology, Biochemistry and Molecular Genetics, Rutgers, the State University of New Jersey, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, Phone: 973 972 4033, christak@ 123456njms.rutgers.edu
          Article
          PMC6814306 PMC6814306 6814306 nihpa993373
          10.1002/jcp.27702
          6814306
          30387140
          35a55470-26b0-4789-9acc-aa82924d1592
          History
          Categories
          Article

          Brahma-related gene 1,histone acetylation,PU.1,cathelicidin,1,25-dihydroxyvitamin D3 ,protein arginine methyltransferase 5

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