Strandberg Karin, Palmberg Lena, Larsson Kjell
Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Respir Med. 2007 Jun;101(6):1132-9. doi: 10.1016/j.rmed.2006.11.014. Epub 2007 Jan 16.
Beta(2)-adrenoceptors are widely distributed and occur on airway epithelial cells. The aim of this study was to find out whether the two long-acting beta(2)-agonists formoterol and salmeterol influence interleukin-6 (IL-6) and -8 (IL-8) release from airway epithelial cells in vitro. A549 cells and primary bronchial epithelial cells (PBEC) were stimulated with organic dust from pig barns. Non-stimulated and dust-stimulated cells were incubated for 24h with formoterol or salmeterol (10(-13)-10(-6)M) and the release of IL-6 and IL-8 into the medium was assessed by ELISA technique. Propranolol (10(-5)M) or sotalol (10(-3)M) were used to block the beta(2)-agonist mediated effects. Formoterol and salmeterol both induced enhancement of IL-6 and IL-8 release and added to the effect of organic dust. This enhanced release was blocked by a beta-blocker in PBEC but not in A549 cells. To our knowledge, this is the first time beta(2)-agonists have been shown to stimulate IL-6 release from airway epithelial cells. The results indicate different mechanisms of beta(2)-agonist action in bronchial and alveolar epithelial cells. Furthermore, our results indicate that A549 cells do not possess functional beta(2)-adrenoceptors.
β₂肾上腺素受体分布广泛,存在于气道上皮细胞上。本研究的目的是探究两种长效β₂激动剂福莫特罗和沙美特罗是否会在体外影响气道上皮细胞白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的释放。用猪舍有机粉尘刺激A549细胞和原代支气管上皮细胞(PBEC)。未刺激和粉尘刺激的细胞分别与福莫特罗或沙美特罗(10⁻¹³ - 10⁻⁶M)孵育24小时,采用酶联免疫吸附测定(ELISA)技术评估IL-6和IL-8释放到培养基中的情况。使用普萘洛尔(10⁻⁵M)或索他洛尔(10⁻³M)阻断β₂激动剂介导的效应。福莫特罗和沙美特罗均诱导IL-6和IL-8释放增加,并增强了有机粉尘的作用。这种增强的释放可被PBEC中的β受体阻滞剂阻断,但在A549细胞中未被阻断。据我们所知,这是首次表明β₂激动剂可刺激气道上皮细胞释放IL-6。结果表明β₂激动剂在支气管和肺泡上皮细胞中的作用机制不同。此外,我们的结果表明A549细胞不具有功能性β₂肾上腺素受体。