RESUMEN
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.
Asunto(s)
Células Epiteliales/inmunología , Receptores de Leucotrieno B4/inmunología , Fumar/inmunología , Western Blotting , Bronquios/citología , Bronquios/inmunología , Bronquios/metabolismo , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Adhesión Celular/efectos de los fármacos , Adhesión Celular/inmunología , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Citometría de Flujo , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/inmunología , Molécula 1 de Adhesión Intercelular/metabolismo , Neutrófilos/citología , Neutrófilos/inmunología , Neutrófilos/metabolismo , PPAR alfa/genética , PPAR alfa/inmunología , PPAR alfa/metabolismo , Extractos Vegetales/inmunología , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Unión Proteica/inmunología , Interferencia de ARN , Receptores de Leucotrieno B4/genética , Receptores de Leucotrieno B4/metabolismo , Factor de Transcripción STAT1/inmunología , Factor de Transcripción STAT1/metabolismo , Fumar/metabolismo , Nicotiana/químicaRESUMEN
Atrial natriuretic peptide, oxytocin and vasopressin are three well known and widely studied molecules since many years. They have been fully characterised from a genetic and biomolecular point of view and a number of receptor-dependent functions have been recognised for them. Nevertheless, in the last years our group has conducted morphologic studies, using an immunohistochemical approach complemented by molecular biology techniques, and could show non-canonical localization and co-localization of these peptides in normal and pathologic tissues, that permitted us to postulate that they may be involved in a wider range of functions than usually assumed and not yet fully understood. In this minireview we summarise some of the main results that open new scenarios in the comprehension of the biologic activities of these peptides and allow to postulate a role for them as diagnostic tools.