Saltar al contenido
Merck
  • Aryl hydrocarbon receptor (AhR) attenuation of subchronic cigarette smoke-induced pulmonary neutrophilia is associated with retention of nuclear RelB and suppression of intercellular adhesion molecule-1 (ICAM-1).

Aryl hydrocarbon receptor (AhR) attenuation of subchronic cigarette smoke-induced pulmonary neutrophilia is associated with retention of nuclear RelB and suppression of intercellular adhesion molecule-1 (ICAM-1).

Toxicological sciences : an official journal of the Society of Toxicology (2014-04-23)
Angela Rico de Souza, Michela Zago, David H Eidelman, Qutayba Hamid, Carolyn J Baglole
RESUMEN

Cigarette smoke is associated with chronic and enhanced pulmonary inflammation characterized by increased cytokine production and leukocyte recruitment to the lung. Although the aryl hydrocarbon receptor (AhR) is well-known to mediate toxic effects of manmade environmental contaminants, the AhR has emerged as a suppressor of acute cigarette smoke-induced neutrophilia by a mechanism involving the NF-κB protein RelB. Yet individuals who smoke often smoke for many years and vary in their cigarette consumption. As there is currently no information on the AhR prevention of lung inflammation, including neutrophilia, due to varied and prolonged exposure regimes, we exposed control and AhR(-/-) mice to cigarette smoke for 2 weeks (subchronic exposure) utilizing low and high exposure protocols and evaluated pulmonary inflammation. Subchronic cigarette smoke exposure significantly increased pulmonary neutrophilia dose-dependently in AhR(-/-) mice. Surprisingly, there was no difference between smoke-exposed AhR(+/-) and AhR(-/-) mice in the expression of cytokines associated with neutrophil recruitment. Expression of pulmonary intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule involved in neutrophil migration and retention, was higher in pulmonary endothelial cells from AhR(-/-) mice. Although total lung RelB expression was increased by cigarette smoke, nuclear RelB was significantly lower in subchronically exposed AhR(-/-) mice. Inhibition of AhR activity by CH-223191 in endothelial cells potentiated ICAM-1 expression and prevented RelB nuclear translocation but had no effect on neutrophil adhesion. These data support that genetic absence of the AhR contributes to heightened pulmonary neutrophilia in response to ongoing cigarette smoke exposure. Interindividual variations in AhR expression may enhance the susceptibility to cigarette smoke-induced diseases.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Fluoruro de fenilmetansulfonilo, ≥98.5% (GC)
Sigma-Aldrich
2,2,2-Tribromoethanol, 97%
Sigma-Aldrich
Selenium, powder, −100 mesh, 99.99% trace metals basis
Sigma-Aldrich
Selenium, powder, −100 mesh, ≥99.5% trace metals basis
Sigma-Aldrich
Fluoruro de fenilmetansulfonilo, ≥99.0% (T)
Sigma-Aldrich
Calcein-AM, suitable for fluorescence, BioReagent, ≥95.0% (HPLC)
Sigma-Aldrich
Nitrogen, ≥99.998%
Sigma-Aldrich
Selenium, pellets, <5 mm, ≥99.99% trace metals basis
Sigma-Aldrich
Selenium, pellets, <5 mm particle size, ≥99.999% trace metals basis
Sigma-Aldrich
Calcein AM solution, 4 mM in DMSO, ≥90% (HPLC), solution
Sigma-Aldrich
4-Thiazolecarboxylic acid, 97%
Selenium, foil, 25x25mm, thickness 3mm, 99.95%
Selenium, pellets, < 5mm, ≥99.999%