1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease Patients.

Haihua Yang,Ning Zhu,Youzhi Zhang,Feng Long,Liang Dong,Xianqiao Jin,Shuijun Li,Ronghuan Yu,Xiaodong Chen,Jingwen Xia,Peng Zhang,Yi Gong,Wenjing Li,Ying Huang,James D Chalmers

doi:10.1371/journal.pone.0120515

Abstract

BackgroundReduced 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.MethodsThe 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.ResultsThe 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.ConclusionOur results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.

Highlights

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality throughout the world, is characterized by persistent airflow limitation and airway and systemic inflammation responses [1]
The 25-(OH) D levels were lower in acute exacerbation chronic obstructive pulmonary disease (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 mitogen-activated protein kinase (MAPK) in peripheral blood neutrophils of AECOPD patients
Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients

Summary

Introduction

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality throughout the world, is characterized by persistent airflow limitation and airway and systemic inflammation responses [1]. Increasing evidence indicates that the p38 MAPK signaling pathway plays an important role in COPD pathogenesis, including chronic inflammation, cell chemotaxis, airway wall remodeling, corticosteroid insensitivity, and airflow obstruction [7,8,9]. The correlation between the P38 MAPK signaling pathway and the apoptosis of peripheral blood neutrophils in COPD is insufficient. Further studies focusing on the p38 MAPK signaling pathway and peripheral blood neutrophil apoptosis in COPD are necessary. Reduced neutrophil apoptosis plays an important role in the pathogenesis of acute exacerbation chronic obstructive pulmonary disease (AECOPD). 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

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Conclusion