Molecular biological mechanism of alcohol-induced asthma

酒精诱发哮喘的分子生物学机制

• 批准号: 12670563
• 负责人: KOHNO Shigeru
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670563/
• 关键词: alcohol-induced asthma; acetaldehyde; GM-CSF; NF-κB; アルコール; 喘息; 肥満細胞; 気管支喘息; アルコール誘発喘息

Approximately half of Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the first study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and investigate the mechanism of such action. Human lung tissue samples were prepared from resected lungs of patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the released chemical mediators. Acetaldehyde (>3x10^<>-4M) increased a … More irway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B2 or cysteinyl-leukotrienes. A histamine antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells, and degranulation of mast cells. The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, and this histamine may be involved in bronchial smooth muscle contraction following alcohol consumption. Acetaldehyde is also found in cigarette smoke and may cause airway inflammation. The purpose of the second study was to determine the effect of acetaldehyde on cytokine production and NF-κB activation in human bronchial tissues. Human bronchi were prepared from normal parts of lung tissues resected for lung cancer. The bronchi were cultured in the presence of 5x10^<-4>M of acetaldehyde for 24 hours and the concentrations of eotaxm, GM-CSF, IL-5, IL-8 and RANTES in cultured supernatants were determined by ELISA. Tissues were also immunohistochemically stained for NF-κBp65. Acetaldehyde significantly increased GM-CSF production from human bronchi and nuclear translocation of NF-κBp65 in airway epithelium, but had no effects on other cytokines. Our findings suggest that acetaldehyde potentially causes airway inflammation via increased GM-CSF production through nuclear translocation of NF-κB. Less

大约一半的日本哮喘患者在饮酒后哮喘加重。我们先前报道，这种现象可能是由于乙醛刺激肥大细胞释放组胺所致。然而，还没有报道描述乙醛对人呼吸道肥大细胞的影响。第一项研究的目的是证明乙醛诱导的人气道肥大细胞释放组胺，并随后引起气道平滑肌收缩，并探讨其作用机制。人肺组织标本取自肺癌患者切除的肺组织。测定乙醛刺激前后对气道肌张力和脏器浴中化学介质释放浓度的影响。用免疫磁法从肺实质中制备肥大细胞，用乙醛刺激后测定释放的化学介质。乙醛(&gt；3x10^&lt；&gt；-4M)增加了…更多虹膜肌张力，这与组胺的释放显著增加有关，但与血栓素B2或半胱氨酰白三烯无关。组胺拮抗剂可完全抑制乙醛诱导的支气管平滑肌收缩。乙醛还能显著诱导人肺肥大细胞释放组胺，并使肥大细胞脱颗粒。本研究结果有力地提示乙醛刺激人呼吸道肥大细胞释放组胺，这种组胺可能与饮酒后的支气管平滑肌收缩有关。在香烟烟雾中也发现了乙醛，可能会引起呼吸道炎症。第二项研究的目的是确定乙醛对人支气管组织细胞因子产生和核因子-κB激活的影响。人的支气管取自肺癌切除的肺组织的正常部分。用含5×10~(-4)~(-4)~(gt；M)乙醛的培养液培养24小时，用双抗体夹心法测定培养上清液中嗜酸粒细胞集落刺激因子、GM-CSF、IL-5、IL-8和RANTES的浓度。用免疫组织化学方法检测组织中NF-κBp65的表达。乙醛可显著增加人支气管分泌GM-κ和呼吸道上皮细胞中的核转位，但对其他细胞因子无明显影响。我们的研究结果表明，乙醛可能通过增加核因子κB的核转位而增加GM-csf的产生，从而导致呼吸道炎症。

项目成果

町田郁子, 松瀬厚人, 河野茂ほか: "Acetaldehyde induces GM-CSF production in human bronchi through activation of nuclear factor-kappa B."Allergy and Asthma Proceedings.. 24・5. 367-371 (2003)

Ikuko Machida、Atsuto Matsuse、Shigeru Kono 等：“乙醛通过核因子 Kappa B 的激活诱导人支气管中 GM-CSF 的产生。过敏和哮喘论文集.. 367-371 (2003)。

河野哲也, 松瀬厚人, 河野茂ほか: "Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction."International Archives of Allergy and Clinical Immunology. In press. (2004)

Tetsuya Kono、Atsuto Matsuse、Shigeru Kono 等人：“乙醛诱导人体气道肥大细胞释放组胺，导致支气管收缩。”国际过敏与临床免疫学档案（2004 年）。

I Machida, H Matsuse, S Kohno, et al.: "Acetaldehyde induces GM-CSF production in human bronchi through activation of nuclear factor-kappa B."Allergy and Asthma Proceedings. 24-5. 367-371 (2003)

I Machida、H Matsuse、S Kohno 等人：“乙醛通过核因子 kappa B 的激活诱导人支气管中 GM-CSF 的产生。”过敏和哮喘论文集。

T Kawano, H Matsuse, S Kohno, et al.: "Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction."International Archives of Allergy and Clinical Immunology. (in press). (2004)

T Kawano、H Matsuse、S Kohno 等人：“乙醛诱导人气道肥大细胞释放组胺，导致支气管收缩。”国际过敏与临床免疫学档案。

町田郁子, 松瀬厚人, 河野 茂ほか: "Aceteldehyde induces GM-CSF production in human bronchi through activation of nuclear factor-kappa B"Allergy and Asthma Proceedings. 24・5. 367-371 (2003)

Ikuko Machida、Atsuto Matsuse、Shigeru Kono 等：“乙醛通过核因子 Kappa B 的激活诱导人支气管中 GM-CSF 的产生”过敏和哮喘论文集 24・5。