beta2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells.

beta2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells.
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DOI:
10.1186/1471-2466-10-30
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发表时间:
2010-05-14
影响因子:
3.1
通讯作者:
Chu HW
Chu HW
中科院分区:
医学3区
文献类型:
--
作者:
Gross CA;Bowler RP;Green RM;Weinberger AR;Schnell C;Chu HW

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气道上皮细胞在慢性阻塞性肺疾病(COPD)和哮喘中对包括肺炎支原体(Mp)在内的细菌的宿主防御中至关重要。β2受体激动剂是治疗COPD和哮喘的主要药物,但β2受体激动剂是否直接影响气道上皮细胞的防御功能尚不清楚。将来自正常(n = 8)、哮喘(n = 8)和COPD(n = 8)受试者的支气管刷拭的上皮细胞在气液界面培养物中生长,并用香烟烟雾提取物(CSE)和/或Th 2细胞因子IL-13处理,随后进行MP感染和用β2-激动剂沙丁胺醇和福莫特罗处理长达7天。对MP和宿主防御蛋白短腭、肺和鼻上皮克隆1(SPLUNC 1)和β-防御素-2进行定量。实时定量RT-PCR检测β2-肾上腺素能受体的表达。(R)-或外消旋沙丁胺醇和(R,R)-或外消旋福莫特罗显著降低正常和哮喘上皮细胞中的MP水平。用MP和(R)-或外消旋沙丁胺醇处理的正常细胞显示SPLUNC 1增加,但β-防御素-2没有增加。COPD细胞对药物治疗没有反应,Mp显著降低或SPLUNC 1增加。IL-13可减弱药物对Mp的作用,并显著降低SPLUNC 1和β2肾上腺素能受体。这些结果首次表明,β2-激动剂增强了正常和哮喘受试者的原代支气管上皮细胞的宿主防御功能,而IL-13减弱了这种功能。
Airway epithelial cells are critical in host defense against bacteria including Mycoplasma pneumoniae (Mp) in chronic obstructive pulmonary disease (COPD) and asthma. β2-agonists are mainstay of COPD and asthma therapy, but whether β2-agonists directly affect airway epithelial host defense functions is unclear. Epithelial cells from bronchial brushings of normal (n = 8), asthma (n = 8) and COPD (n = 8) subjects were grown in air-liquid interface cultures, and treated with cigarette smoke extract (CSE) and/or Th2 cytokine IL-13, followed by Mp infection and treatment with β2-agonists albuterol and formoterol for up to seven days. Mp and host defense proteins short palate, lung, and nasal epithelial clone 1 (SPLUNC1) and β-defensin-2 were quantified. Expression of β2-adrenergic receptors was also measured by real-time quantitative RT-PCR. (R)- or racemic albuterol and (R,R)- or racemic formoterol significantly decreased Mp levels in normal and asthma epithelial cells. Normal cells treated with Mp and (R)- or racemic albuterol showed an increase in SPLUNC1, but not in β-defensin-2. COPD cells did not respond to drug treatment with a significant decrease in Mp or an increase in SPLUNC1. IL-13 attenuated drug effects on Mp, and markedly decreased SPLUNC1 and β2-adrenergic receptors. These results for the first time show that β2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which is attenuated by IL-13.
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