title: Enhanced LL-37 expression following vitamin D supplementation in patients with cirrhosis and spontaneous bacterial peritonitis.
abstract: OBJECTIVE
  The morbidity and mortality of spontaneous bacterial peritonitis (SBP) are high among patients with cirrhosis; however, the mechanisms of SBP pathogenesis are poorly understood. This study aimed to determine the role of the vitamin D-LL-37 pathway in the pathogenesis and treatment in patients with cirrhosis and SBP.
  
  
  METHODS
  Serum 25-hydroxyvitamin D concentrations of 119 patients with chronic liver diseases were tested. Vitamin D receptor (VDR) and LL-37 in peritoneal leucocytes of cirrhotic and ascitic patients with SBP were detected and compared with those without SBP. Then the peritoneal macrophages of non-infected patients were cultured and activated by lipopolysaccharide (LPS) to analyse the changes of VDR and LL-37 expressions after incubation with vitamin D.
  
  
  RESULTS
  Vitamin D deficiency or insufficiency was found in all of patients with cirrhosis. LPS inhibited VDR and LL-37 expression in peritoneal macrophages [1.3-fold decrease (P = 0.003) and 20-fold decrease (P = 0.010) respectively]. However, vitamin D could reverse the inhibition of both VDR and LL-37 [1.5-fold increase (P = 0.001) and 2000-fold increase (P < 0.001) respectively]. The effect of the incubation time following vitamin D supplementation was significant for LL-37 expression, with a peak expression found at 36 h (P < 0.001).
  
  
  CONCLUSIONS
  When vitamin D levels were low, bacteria inhibited VDR and LL-37 responses in peritoneal macrophages as a mechanism to evade antibacterial defence. Vitamin D supplementation could up-regulate peritoneal macrophage VDR and LL-37 expressions, which resulted in an enhanced immunological defence against SBP in patients with cirrhosis and ascites.
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Lianrong
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Han
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Ziying
authors.initials: Z
authors.lastname: An
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Dou
mesh_terms: D000328:Adult; D001201:Ascites / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001202:Ascitic Fluid / Q000378:metabolism / Q000473:pathology; D001424:Bacterial Infections / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018407:Bacterial Physiological Phenomena; D054804:Cathelicidins / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D010538:Peritonitis / Q000209:etiology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018167:Receptors, Calcitriol / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000150:complications / Q000378:metabolism / Q000473:pathology; D014815:Vitamins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D054804:Cathelicidins; D010446:Peptide Fragments; D018167:Receptors, Calcitriol; D014815:Vitamins; C534394:cathelicidin LL-37 (18-29), human; D014807:Vitamin D
keywords: LL-37; peritoneal macrophages; spontaneous bacterial peritonitis; vitamin D