Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence.
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.
Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy. pace@ibim.cnr.it
Elisabetta
E
Pace
Maria
M
Ferraro
Serena
S
Di Vincenzo
Andreina
A
Bruno
Antonino
A
Giarratano
Valeria
V
Scafidi
Luana
L
Lipari
Denise Valentina
DV
Di Benedetto
Serafina
S
Sciarrino
Mark
M
Gjomarkaj
D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D034622:RNA Interference; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism; D012907:Smoking / Q000276:immunology* / Q000378:metabolism; D014026:Nicotiana / Q000737:chemistry
C485878:LTB4R2 protein, human; D047493:PPAR alpha; D010936:Plant Extracts; D018102:Receptors, Leukotriene B4; D050794:STAT1 Transcription Factor; D018799:Intercellular Adhesion Molecule-1