IR@PKUHSC  > 北京大学第一临床医学院  > 皮肤性病科
学科主题临床医学
CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema
Shigeta, Ayako; Tada, Yuji1; Wang, Ji-Yang4; Ishizaki, Shunsuke; Tsuyusaki, Junichi; Yamauchi, Keita; Kasahara, Yasunori; Iesato, Ken; Tanabe, Nobuhiro; Takiguchi, Yuichi2; Sakamoto, Akemi3; Tokuhisa, Takeshi3; Shibuya, Kazutoshi5,6; Hiroshima, Kenzo7; West, James8; Tatsumi, Koichiro
关键词alveolus inflammation IFN-gamma chemokine regulated on activation normal T cells expressed and secreted (RANTES)
刊名AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
2012-07-01
DOI10.1152/ajplung.00337.2011
303期:2页:L141-L151
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Physiology ; Respiratory System
研究领域[WOS]Physiology ; Respiratory System
关键词[WOS]OBSTRUCTIVE PULMONARY-DISEASE ; SMOKE-INDUCED EMPHYSEMA ; ENDOTHELIAL-CELLS ; UP-REGULATION ; LIGAND CD154 ; SOLUBLE FAS ; MOUSE LUNG ; INFLAMMATION ; COPD ; MICE
英文摘要

Shigeta A, Tada Y, Wang J-Y, Ishizaki S, Tsuyusaki J, Yamauchi K, Kasahara Y, Iesato K, Tanabe N, Takiguchi Y, Sakamoto A, Tokuhisa T, Shibuya K, Hiroshima K, West J, Tatsumi K. CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema. Am J Physiol Lung Cell Mol Physiol 303: L141-L151, 2012. First published May 18, 2012; doi:10.1152/ajplung.00337.2011.-Excessive apoptosis and prolonged inflammation of alveolar cells are associated with the pathogenesis of pulmonary emphysema. We aimed to determine whether CD40 affects alveolar epithelial cells and endothelial cells, with regard to evoking apoptosis and inflammation. Mice were repeatedly treated with agonistic-anti CD40 antibody (Ab), with or without agonistic-anti Fas Ab, and evaluated for apoptosis and inflammation in lungs. Human pulmonary microvascular endothelial cells and alveolar epithelial cells were treated with agonistic anti-CD40 Ab and/or anti-Fas Ab to see their direct effect on apoptosis and secretion of proinflammatory molecules in vitro. Furthermore, plasma soluble CD40 ligand (sCD40L) level was evaluated in patients with chronic obstructive pulmonary disease (COPD). In mice, inhaling agonistic anti-CD40 Ab induced moderate alveolar enlargement. CD40 stimulation, in combination with anti-Fas Ab, induced significant emphysematous changes and increased alveolar cell apoptosis. CD40 stimulation also enhanced IFN-gamma-mediated emphysematous changes, not via apoptosis induction, but via inflammation with lymphocyte accumulation. In vitro, Fas-mediated apoptosis was enhanced by CD40 stimulation and IFN-gamma in endothelial cells and by CD40 stimulation in epithelial cells. CD40 stimulation induced secretion of CCR5 ligands in endothelial cells, enhanced with IFN-gamma. Plasma sCD40L levels were significantly increased in patients with COPD, inversely correlating to the percentage of forced expiratory volume in 1 s and positively correlating to low attenuation area score by CT scan, regardless of smoking history. Collectively CD40 plays a contributing role in the development of pulmonary emphysema by sensitizing Fas-mediated apoptosis in alveolar cells and increasing the secretion of proinflammatory chemokines.

语种英语
WOS记录号WOS:000306415500006
项目编号23591114 ; H22-Shinko-Ippan-008 ; H23-Shinko-Ippan-018
资助机构Ministry of Education, Science, Sports and Culture ; Ministry of Health, Labor and Welfare of Japan ; Ministry of Education, Culture, Sports, Science and Technology of Japan ; Strategic Research Foundation
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62063
专题北京大学第一临床医学院_皮肤性病科
作者单位1.Chiba Univ, Grad Sch Med, Dept Dev Genet, Chiba 2608670, Japan
2.Toho Univ, Sch Med, Dept Pathol, Tokyo, Japan
3.Chiba Univ, Grad Sch Med, Dept Med Oncol, Chiba 2608670, Japan
4.Chiba Univ, Grad Sch Med, Dept Respirol, Chuo Ku, Chiba 2608670, Japan
5.RIKEN Yokohama Inst, Res Ctr Allergy & Immunol, Lab Immune Div, Yokohama, Kanagawa, Japan
6.Peking Univ, Hosp 1, Dept Dermatol, Beijing 100871, Peoples R China
7.Tokyo Womens Med Univ, Yachiyo Med Ctr, Dept Pathol, Chiba, Japan
8.Vanderbilt Univ, Div Allergy Pulm & Crit Care Med, Nashville, TN USA
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GB/T 7714
Shigeta, Ayako,Tada, Yuji,Wang, Ji-Yang,et al. CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema[J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2012,303(2):L141-L151.
APA Shigeta, Ayako.,Tada, Yuji.,Wang, Ji-Yang.,Ishizaki, Shunsuke.,Tsuyusaki, Junichi.,...&Tatsumi, Koichiro.(2012).CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,303(2),L141-L151.
MLA Shigeta, Ayako,et al."CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 303.2(2012):L141-L151.
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