title: Vitamin D-dependent cathelicidin inhibits Mycobacterium marinum infection in human monocytic cells.
abstract: 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.
authors: Department of Dermatology, Fukuoka University School of Medicine, Fukuoka, Japan. emi_sato1982@yahoo.co.jp
authors: Emi
authors: E
authors: Sato
authors: Shinichi
authors: S
authors: Imafuku
authors: Kazunari
authors: K
authors: Ishii
authors: Ryota
authors: R
authors: Itoh
authors: Bin
authors: B
authors: Chou
authors: Toshinori
authors: T
authors: Soejima
authors: Juichiro
authors: J
authors: Nakayama
authors: Kenji
authors: K
authors: Hiromatsu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D019910:Mycobacterium marinum / Q000187:drug effects*; D034622:RNA Interference; D018167:Receptors, Calcitriol / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D016207:Cytokines; D008869:Microtubule-Associated Proteins; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C025946:3-methyladenine; D002738:Chloroquine; D002117:Calcitriol; D000225:Adenine; D054804:Cathelicidins