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

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 tumo...

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Veröffentlicht in:PloS one 2015-04, Vol.10 (4), p.e0120515-e0120515
Hauptverfasser: Yang, Haihua, Long, Feng, Zhang, Youzhi, Yu, Ronghuan, Zhang, Peng, Li, Wenjing, Li, Shuijun, Jin, Xianqiao, Xia, Jingwen, Dong, Liang, Zhu, Ning, Huang, Ying, Gong, Yi, Chen, Xiaodong
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container_issue 4
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container_title PloS one
container_volume 10
creator Yang, Haihua
Long, Feng
Zhang, Youzhi
Yu, Ronghuan
Zhang, Peng
Li, Wenjing
Li, Shuijun
Jin, Xianqiao
Xia, Jingwen
Dong, Liang
Zhu, Ning
Huang, Ying
Gong, Yi
Chen, Xiaodong
description 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. 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. 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. Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.
doi_str_mv 10.1371/journal.pone.0120515
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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. 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. 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. Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0120515</identifier><identifier>PMID: 25905635</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>25-Hydroxyvitamin D ; Aged ; Apoptosis ; Apoptosis - drug effects ; Blood ; Case-Control Studies ; Chromatography ; Chronic obstructive pulmonary disease ; Correlation ; Correlation analysis ; Correlation coefficient ; Correlation coefficients ; Dihydroxyvitamin D3 ; Female ; Flow cytometry ; Flow mapping ; Humans ; Imidazoles - therapeutic use ; Kinases ; Leukocytes (neutrophilic) ; Liquid chromatography ; Lung diseases ; Male ; MAP kinase ; Mass spectrometry ; Mass spectroscopy ; Neutrophils - drug effects ; Neutrophils - metabolism ; Obstructive lung disease ; p38 Mitogen-Activated Protein Kinases - metabolism ; Pathogenesis ; Patients ; Peripheral blood ; Phosphorylation - drug effects ; Protein kinase ; Proteins ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - metabolism ; Pyridines - therapeutic use ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Statistical analysis ; Statistical methods ; Studies ; Variance analysis ; Vitamin D ; Vitamin D - analogs &amp; derivatives ; Vitamin D - therapeutic use ; Vitamin D3</subject><ispartof>PloS one, 2015-04, Vol.10 (4), p.e0120515-e0120515</ispartof><rights>2015 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Yang et al 2015 Yang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4925-14d5a49fbbc9ab3405fbc2c6ab15be36562a84eea0af14500a2495c5cb318343</citedby><cites>FETCH-LOGICAL-c4925-14d5a49fbbc9ab3405fbc2c6ab15be36562a84eea0af14500a2495c5cb318343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407887/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407887/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25905635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Haihua</creatorcontrib><creatorcontrib>Long, Feng</creatorcontrib><creatorcontrib>Zhang, Youzhi</creatorcontrib><creatorcontrib>Yu, Ronghuan</creatorcontrib><creatorcontrib>Zhang, Peng</creatorcontrib><creatorcontrib>Li, Wenjing</creatorcontrib><creatorcontrib>Li, Shuijun</creatorcontrib><creatorcontrib>Jin, Xianqiao</creatorcontrib><creatorcontrib>Xia, Jingwen</creatorcontrib><creatorcontrib>Dong, Liang</creatorcontrib><creatorcontrib>Zhu, Ning</creatorcontrib><creatorcontrib>Huang, Ying</creatorcontrib><creatorcontrib>Gong, Yi</creatorcontrib><creatorcontrib>Chen, Xiaodong</creatorcontrib><title>1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease Patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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. 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. 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. Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.</description><subject>25-Hydroxyvitamin D</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Blood</subject><subject>Case-Control Studies</subject><subject>Chromatography</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Correlation</subject><subject>Correlation analysis</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Dihydroxyvitamin D3</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Flow mapping</subject><subject>Humans</subject><subject>Imidazoles - therapeutic use</subject><subject>Kinases</subject><subject>Leukocytes (neutrophilic)</subject><subject>Liquid chromatography</subject><subject>Lung diseases</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - metabolism</subject><subject>Obstructive lung disease</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Phosphorylation - drug effects</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary Disease, Chronic Obstructive - metabolism</subject><subject>Pyridines - therapeutic use</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Studies</subject><subject>Variance analysis</subject><subject>Vitamin D</subject><subject>Vitamin D - analogs &amp; 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Long, Feng ; Zhang, Youzhi ; Yu, Ronghuan ; Zhang, Peng ; Li, Wenjing ; Li, Shuijun ; Jin, Xianqiao ; Xia, Jingwen ; Dong, Liang ; Zhu, Ning ; Huang, Ying ; Gong, Yi ; Chen, Xiaodong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4925-14d5a49fbbc9ab3405fbc2c6ab15be36562a84eea0af14500a2495c5cb318343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>25-Hydroxyvitamin D</topic><topic>Aged</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Blood</topic><topic>Case-Control Studies</topic><topic>Chromatography</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Correlation</topic><topic>Correlation analysis</topic><topic>Correlation coefficient</topic><topic>Correlation coefficients</topic><topic>Dihydroxyvitamin D3</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Flow mapping</topic><topic>Humans</topic><topic>Imidazoles - therapeutic use</topic><topic>Kinases</topic><topic>Leukocytes (neutrophilic)</topic><topic>Liquid chromatography</topic><topic>Lung diseases</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - metabolism</topic><topic>Obstructive lung disease</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Phosphorylation - drug effects</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Pulmonary Disease, Chronic Obstructive - drug therapy</topic><topic>Pulmonary Disease, Chronic Obstructive - metabolism</topic><topic>Pyridines - therapeutic use</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signaling</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Studies</topic><topic>Variance analysis</topic><topic>Vitamin D</topic><topic>Vitamin D - analogs &amp; 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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Haihua</au><au>Long, Feng</au><au>Zhang, Youzhi</au><au>Yu, Ronghuan</au><au>Zhang, Peng</au><au>Li, Wenjing</au><au>Li, Shuijun</au><au>Jin, Xianqiao</au><au>Xia, Jingwen</au><au>Dong, Liang</au><au>Zhu, Ning</au><au>Huang, Ying</au><au>Gong, Yi</au><au>Chen, Xiaodong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease Patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-04-23</date><risdate>2015</risdate><volume>10</volume><issue>4</issue><spage>e0120515</spage><epage>e0120515</epage><pages>e0120515-e0120515</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. 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. 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. Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25905635</pmid><doi>10.1371/journal.pone.0120515</doi><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects 25-Hydroxyvitamin D
Aged
Apoptosis
Apoptosis - drug effects
Blood
Case-Control Studies
Chromatography
Chronic obstructive pulmonary disease
Correlation
Correlation analysis
Correlation coefficient
Correlation coefficients
Dihydroxyvitamin D3
Female
Flow cytometry
Flow mapping
Humans
Imidazoles - therapeutic use
Kinases
Leukocytes (neutrophilic)
Liquid chromatography
Lung diseases
Male
MAP kinase
Mass spectrometry
Mass spectroscopy
Neutrophils - drug effects
Neutrophils - metabolism
Obstructive lung disease
p38 Mitogen-Activated Protein Kinases - metabolism
Pathogenesis
Patients
Peripheral blood
Phosphorylation - drug effects
Protein kinase
Proteins
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - metabolism
Pyridines - therapeutic use
Signal transduction
Signal Transduction - drug effects
Signaling
Statistical analysis
Statistical methods
Studies
Variance analysis
Vitamin D
Vitamin D - analogs & derivatives
Vitamin D - therapeutic use
Vitamin D3
title 1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease Patients
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