title: Vitamin D differentially regulatesSalmonella-induced intestine epithelial autophagy and interleukin-1β expression.
abstract: OBJECTIVE
  To investigate the effects of active vitamin D3 on autophagy and interleukin (IL)-1β expression inSalmonella-infected intestinal epithelial cells (IECs).
  
  
  METHODS
  Caco-2 cells, NOD2 siRNA-, Atg16L1 siRNA- or vitamin D receptor (VDR) siRNA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3 (1,25D3), and then infected by wild-typeS. typhimuriumstrain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR siRNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and mRNA expression, respectively. Atg16L1 siRNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mRNA expression.
  
  
  RESULTS
  The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mRNA expression, membranous Atg16L1 protein expression leading to enhanced autophagic LC3II protein expression and LC3 punctae inSalmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR siRNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression inSalmonella-infected IECs.
  
  
  CONCLUSIONS
  Active vitamin D might enhance autophagic clearance ofSalmonellainfection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.
authors.affiliation: Fu-Chen Huang, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
authors.forename: Fu-Chen
authors.initials: FC
authors.lastname: Huang
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012480:Salmonella Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: C518959:ATG16L1 protein, human; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000071183:Autophagy-Related Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D002117:Calcitriol
keywords: Atg16L1; Autophagy; Interleukin-1β; Intestinal epithelia; Salmonella; Vitamin D