title: 1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease Patients.
abstract: BACKGROUND
  Reduced neutrophil apoptosis plays an important role in the pathogenesis of acute exacerbation chronic obstructive pulmonary disease (AECOPD). The p38 mitogen-activated protein kinase (MAPK) signaling pathway is involved in neutrophil apoptosis. 1α,25-Dihydroxyvitamin D3 (1α,25VitD3) can induce tumor cell apoptosis. The aim of this study was to assess the effects of 1α,25VitD3 on peripheral blood neutrophil apoptosis in AECOPD and examine the role of the p38 MAPK signaling pathway.
  
  
  METHODS
  The study enrolled 36 AECOPD patients and 36 healthy volunteers. Venous blood samples were obtained from both groups. Serum 25-hydroxyvitamin D (25-(OH) D) levels in peripheral venous blood were assayed using liquid chromatography-tandem mass spectrometry (LC-MS/MS); the neutrophils were separated and cultured with SB203580 (a p38 inhibitor) and 1α,25VitD3. Neutrophil apoptosis was measured using flow cytometry, and phospho-p38 MAPK protein expression was detected by Western blot. Statistical analysis was performed using analysis of variance. Student's t-test and Pearson's correlation coefficient were used for the between-group differences and correlation analysis, respectively.
  
  
  RESULTS
  The 25-(OH) D levels were lower in AECOPD patients than in healthy controls, and the peripheral blood neutrophil apoptosis results were similar. 1α,25VitD3 increased the apoptosis rate and the level of phospho-p38 MAPK in peripheral blood neutrophils of AECOPD patients. SB203580 partly inhibited 1α,25VitD3-induced peripheral blood neutrophil apoptosis and phospho-p38 MAPK overexpression. The 25-(OH) D levels were positively correlated with increased peripheral blood neutrophil apoptosis and phospho-p38 MAPK levels. In addition, expression of the phospho-p38 MAPK protein was also positively correlated with peripheral blood neutrophil apoptosis.
  
  
  CONCLUSIONS
  Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital North, Fudan University, ShangHai, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital North, Fudan University, ShangHai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital North, Fudan University, ShangHai, China.
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Xuhui Central Hospital, ShangHai, China.
authors.forename: Ronghuan
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital North, Fudan University, ShangHai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital North, Fudan University, ShangHai, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Central Laboratory, Xuhui Central Hospital, ShangHai, China.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, ShangHai, China.
authors.forename: Xianqiao
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, ShangHai, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, ShangHai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, ShangHai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, Xuhui Central Hospital, ShangHai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, ShangHai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, ShangHai, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D011725:Pyridines; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580