A protective role for proteinase activated receptor 2 in airways of lipopolysaccharide-treated rats.
Proteinase activated receptor-2 (PAR2), a seven transmembrane domain G protein coupled receptor, is expressed on airway epithelium and smooth muscle cells and over-expressed in human airways under pathological conditions, such as asthma and chronic obstructive pulmonary disease (COPD). However, the role of PAR2 in airways has not yet been defined. Aim of the present study, was to evaluate the in vitro rat bronchial response to a synthetic peptide activating PAR2 (PAR2-AP; SLIGRL), following an in vivo treatment with bacterial lipopolysaccharide (LPS). Bronchi from LPS-treated animals showed an increased relaxant response to PAR2-AP, compared to naïve animals, the effect was maximum after 20-h pre-treatment and reduced by epithelium removal. Western blot analysis showed an increased PAR2 protein expression on bronchi removed 20h after LPS treatment. PAR2-AP-induced bronchorelaxation was inhibited by ibuprofen, by the selective cyclooxygenase2 (COX-2) inhibitor, diisopropyl fluorophosphate (DFP) and partially by the calcitonin gene related peptide (CGRP) antagonist, rat-CGRP([8-37]). Furthermore, there was a strong immunoreactivity for COX-2 on bronchial epithelium of LPS-treated rats. Prostaglandin E2 (PGE2) tissue release and CGRP tissue content were significantly increased following tissue incubation with PAR2-AP. The in vivo LPS treatment in rats strongly increases the bronchorelaxant effect of PAR2-AP, this effect correlates with an increased tissue protein receptor expression and the COX-2 localization on bronchial epithelium. Our work supports a role for PAR2 as a defence mechanism aimed to preserve bronchial functionality under systemic inflammatory conditions; both COX-2-derived PGE2 and CGRP are involved in this effect.
Morello
Silvana
S
Department of Experimental Pharmacology, University of Naples Federico II, via D. Montesano 49, 80131 Naples, Italy.
Vellecco
Valentina
V
Roviezzo
Fiorentina
F
Maffia
Pasquale
P
Cuzzocrea
Salvatore
S
Cirino
Giuseppe
G
Cicala
Carla
C
D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000502:physiology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D044464:Receptor, PAR-2; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone