Reference - Detail
|Author||Sato E, Imafuku S, Ishii K, Itoh R, Chou B, Soejima T, Nakayama J, Hiromatsu K.|
|Title||Vitamin D-dependent cathelicidin inhibits Mycobacterium marinum infection in human monocytic cells.|
|Journal||J Dermatol Sci|
BACKGROUND:1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates the production of human cathelicidin antimicrobial peptide (CAMP) from monocytes/macrophages infected with Mycobacterium tuberculosis (M. tbc). CAMP facilitates the co-localization of autophagolysosomes with M. tbc, promoting the antimicrobial activity of monocytes. Mycobacterium marinum (M. marinum) is an acid-fast bacillus that causes less severe granulomatous skin lesions compared with M. tbc.
OBJECTIVE:We investigated whether autophagic antimicrobial activity is promoted by 1,25(OH)2D3 or C-terminal of cathelicidin LL-37 in human monocytes upon infection with M. marinum.
METHODS:Human monocytes (THP-1) were infected with M. marinum. Effects of simultaneous treatments of 1,25(OH)2D3, exogenous LL-37 peptide, autophagolysosome inhibitors, 3-methyladenine or chloroquine, were examined.
RESULTS:CAMP was strongly induced by adding 1,25(OH)2D3 to the culture of THP-1 cells. In the absence of 1,25(OH)2D3 M. marinum infection alone did not induce CAMP, however, simultaneous addition of 1,25(OH)2D3 to M. marinum infection accelerated CAMP production more than 1,25(OH)2D3 alone. Proliferation of M. marinum was markedly decreased in the presence of 1,25(OH)2D3 or exogenous LL-37 in THP-1 cells. Co-localization of CAMP with autophagolysosome was evident in 1,25(OH)2D3 and LL-37 treated THP-1 cells after M. marinum infection. Autophagolysosome inhibitors abrogated the antimicrobial effects of 1,25(OH)2D3 and exogenous LL-37 against M. marinum infection in THP-1 cells.
CONCLUSIONS:Human monocytic cells, whose CAMP production is up-regulated by 1,25(OH)2D3-vitamin D receptor pathway, accelerate antimicrobial function of autophagolysosome in M. marinum infection.
|MeSH||Adenine / analogs & derivatives Adenine / pharmacology Animals Anti-Bacterial Agents / pharmacology* Antimicrobial Cationic Peptides / metabolism* Antimicrobial Cationic Peptides / pharmacology Autophagy / drug effects* Autophagy-Related Protein 5 Calcitriol / pharmacology* Cell Line, Tumor Chloroquine / pharmacology Cytokines / metabolism Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / microbiology Humans Mice, Knockout Microtubule-Associated Proteins / deficiency Microtubule-Associated Proteins / genetics Monocytes / drug effects* Monocytes / immunology Monocytes / metabolism Monocytes / microbiology Monocytes / pathology Mycobacterium Infections, Nontuberculous / immunology Mycobacterium Infections, Nontuberculous / metabolism Mycobacterium Infections, Nontuberculous / microbiology Mycobacterium Infections, Nontuberculous / pathology Mycobacterium Infections, Nontuberculous / prevention & control* Mycobacterium marinum / drug effects* RNA Interference Receptors, Calcitriol / agonists Receptors, Calcitriol / genetics Receptors, Calcitriol / metabolism Time Factors Transfection Up-Regulation|
|Human and Animal Cells||Atg5^(-/-)MEF(RCB2711)|