Aryl hydrocarbon receptor attenuation of sub-chronic cigarette smoke-induced pulmonary neutrophilia is associated with retention of nuclear RelB and suppression of intercellular adhesion molecule-1 (CAM1P.233)

Abstract

Abstract Cigarette smoke exposure 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 environmental contaminants, the AhR has emerged as a suppressor of acute cigarette smoke-induced neutrophilia. As there is currently no information on the AhR prevention of lung inflammation due to varied and prolonged exposure regimes, we exposed control and AhR-/- mice to cigarette smoke for 2 weeks (sub-chronic exposure) utilizing low and high exposure protocols and evaluated pulmonary inflammation. Sub-chronic cigarette smoke exposure increased pulmonary neutrophilia dose-dependently in AhR-/- mice. There was no difference between smoke-exposed AhR+/- and AhR-/- mice in the expression of cytokines associated with neutrophil recruitment. However, expression of pulmonary intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule involved in neutrophil migration and retention, was higher in AhR-/- mice. Nuclear RelB, an anti-inflammatory NFkB transcription factor, was significantly lower in sub-chronically exposed AhR-/- mice. These data support that absence of the AhR contributes to heightened pulmonary neutrophilia in response to on-going cigarette smoke exposure. Inter-individual variations in AhR expression may enhance the susceptibility to cigarette smoke induced diseases.