Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy.
Immunology. 2013 Jun;139(2):245-55. doi: 10.1111/imm.12077.
Leukotriene B(4) (LTB(4)) is a neutrophil chemotactic molecule with important involvement in the inflammatory responses of chronic obstructive pulmonary disease (COPD). Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke, the major risk factor for COPD. In this study we have explored whether cigarette smoke extracts (CSE) or soluble mediators present in distal lung fluid samples (mini-bronchoalveolar lavages) from smokers alter the expression of the LTB(4) receptor 2 (BLT2) and peroxisome proliferator-activated receptor-α (PPAR-α) in bronchial epithelial cells. We also evaluated the effects of CSE on the expression of intercellular adhesion molecule 1 (ICAM-1) and on the binding of signal transducer and activator of transcription 1 (STAT-1) to ICAM-1 promoter as well as the adhesiveness of neutrophils to bronchial epithelial cells. CSE and mini-bronchoalveolar lavages from smokers increased BLT2 and ICAM-1 expression as well as the adhesiveness of neutrophils to bronchial epithelial cells and decreased PPAR-α expression. CSE induced the activation of STAT-1 and its binding to ICAM-1 promoter. These findings suggest that, in bronchial epithelial cells, CSE promote a prevalent induction of pro-inflammatory BLT2 receptors and activate mechanisms leading to increased neutrophil adhesion, a mechanism that contributes to airway neutrophilia and to tissue damage.
白三烯 B(4)（LTB(4)）是一种嗜中性粒细胞趋化分子，在慢性阻塞性肺疾病（COPD）的炎症反应中具有重要作用。气道上皮细胞作为一种调节固有免疫反应的机制，可对各种刺激物（包括香烟烟雾，COPD 的主要危险因素）产生反应。在这项研究中，我们探讨了香烟烟雾提取物（CSE）或吸烟者远端肺液样本（微型支气管肺泡灌洗）中存在的可溶性介质是否会改变气道上皮细胞中 LTB(4)受体 2（BLT2）和过氧化物酶体增殖物激活受体-α（PPAR-α）的表达。我们还评估了 CSE 对细胞间黏附分子 1（ICAM-1）表达的影响，以及信号转导和转录激活因子 1（STAT-1）与 ICAM-1 启动子结合的影响，以及中性粒细胞与气道上皮细胞的黏附能力。CSE 和吸烟者的微型支气管肺泡灌洗液增加了 BLT2 和 ICAM-1 的表达，以及中性粒细胞与气道上皮细胞的黏附能力，并降低了 PPAR-α 的表达。CSE 诱导了 STAT-1 的激活及其与 ICAM-1 启动子的结合。这些发现表明，在气道上皮细胞中，CSE 促进了促炎 BLT2 受体的普遍诱导，并激活了导致中性粒细胞黏附增加的机制，这一机制有助于气道中性粒细胞增多和组织损伤。
