Cigarette smoke–induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents
Eunice Andrè, … , Pierangelo Geppetti, Riccardo Patacchini
Eunice Andrè, … , Pierangelo Geppetti, Riccardo Patacchini
Published June 20, 2008
Citation Information: J Clin Invest. 2008;118(7):2574-2582. https://doi.org/10.1172/JCI34886.
View: Text | PDF
Research Article

Cigarette smoke–induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents

Abstract

Cigarette smoke (CS) inhalation causes an early inflammatory response in rodent airways by stimulating capsaicin-sensitive sensory neurons that express transient receptor potential cation channel, subfamily V, member 1 (TRPV1) through an unknown mechanism that does not involve TRPV1. We hypothesized that 2 α,β-unsaturated aldehydes present in CS, crotonaldehyde and acrolein, induce neurogenic inflammation by stimulating TRPA1, an excitatory ion channel coexpressed with TRPV1 on capsaicin-sensitive nociceptors. We found that CS aqueous extract (CSE), crotonaldehyde, and acrolein mobilized Ca2+ in cultured guinea pig jugular ganglia neurons and promoted contraction of isolated guinea pig bronchi. These responses were abolished by a TRPA1-selective antagonist and by the aldehyde scavenger glutathione but not by the TRPV1 antagonist capsazepine or by ROS scavengers. Treatment with CSE or aldehydes increased Ca2+ influx in TRPA1-transfected cells, but not in control HEK293 cells, and promoted neuropeptide release from isolated guinea pig airway tissue. Furthermore, the effect of CSE and aldehydes on Ca2+ influx in dorsal root ganglion neurons was abolished in TRPA1-deficient mice. These data identify α,β-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases.

Authors

Eunice Andrè, Barbara Campi, Serena Materazzi, Marcello Trevisani, Silvia Amadesi, Daniela Massi, Christophe Creminon, Natalya Vaksman, Romina Nassini, Maurizio Civelli, Pier Giovanni Baraldi, Daniel P. Poole, Nigel W. Bunnett, Pierangelo Geppetti, Riccardo Patacchini

×

Figure 5

CS and CSE increase tracheal plasma extravasation.

Options: View larger image (or click on image) Download as PowerPoint
CS and CSE increase tracheal plasma extravasation. Effect of intratrache...
Effect of intratracheal RR (4.5 nmol/150 μl), HC-030031 (45 nmol/150 μl), capsazepine (45 nmol/150 μl), or their respective vehicles (150 μl) on the increase in plasma extravasation produced by (A) CS inhalation (2 puffs = 60 ml) or (B) capsaicin administration (1 μmol/kg, i.v.) in anesthetized guinea pigs. Columns represent the mean ± SEM of a least 4 experiments. Veh0, vehicles of RR, HC, and CPZ; Veh1, vehicle of CPS; Veh2, vehicles of HC and CPZ. *P < 0.05 versus Veh; #P < 0.05 versus Veh2. C shows plasma extravasation evoked by intratracheal instillation of CSE vehicle (WT Veh; 25 μl) or CSE in wild-type or CSE in TRPA1-deficient mice. ΧP < 0.05 versus WT (1-way ANOVA, followed by Bonferroni’s test).