Cigarette smoke alters the expression of the pro-inflammatory LTB4 receptor and increases the neutrophil adhesion in bronchial epithelial cells

LTB4 is importantly involved in the inflammatory responses of chronic obstructive pulmonary disease (COPD). In COPD an increased expression of LTB4 receptors, BLT1 and of PPAR-a, was observed. Since LTB4 is reduced upon TLR4 mutation and since cigarette smoke extracts (CSE) increase the expression of TLR4 in bronchial epithelial cells, the aims of this study were to explore whether CSE with/without LPS (a ligand of TLR4) or mini-BAL supernatants from smokers alter, in bronchial epithelial cells, the expression (evaluated by flow-cytometry analysis) of pro (BLT2) and anti-inflammatory (PPAR-a) LTB4 receptors. Moreover, we evaluated the effects of CSE on the expression of ICAM-1 (by flow-cytometry analysis), on the binding of STAT-1 to ICAM-1 promoter (by ChiP analysis), and on the adhesiveness of bronchial epithelial cells to neutrophils (by fluorimetry). CSE alone increased BLT2 while decreased PPARa expression. The addition of LPS did not modify CSE effects. mini-BAL from smokers increased BLT2 but not PPARa expression. A neutralizing TLR4 antibody reduced the expression of BLT2 but it had no effects in PPAR-a expression. CSE increased the binding of STAT-1 to ICAM-1 promoter and increased the expression of ICAM-1 in bronchial epithelial cells. CSE and mini-BAL from smokers increased the adhesiveness of bronchial epithelial cells toward neutrophils more than mini-BAL from non-smokers. These findings suggest that, in bronchial epithelial cells, CSE promote a prevalent induction of pro-inflammatory BLT2 receptors and activate mechanisms leading to increase neutrophil adhesion, a mechanism contributing to airway neutrophilia.