title: Lung-targeted overexpression of the NF-κB member RelB inhibits cigarette smoke-induced inflammation.
abstract: Acute lung inflammation can be caused by a variety of respirable agents, including cigarette smoke. Long-term cigarette smoke exposure can cause chronic obstructive pulmonary disease (COPD), a serious illness that affects >10 million Americans. Cigarette smoke is a known inducer of inflammation and is responsible for approximately 90% of all COPD cases. RelB, a member of the NF-κB family, attenuates cigarette smoke-induced inflammatory mediator production in mouse lung fibroblasts in vitro. We hypothesized that overexpression of RelB in the airways of mice would dampen acute smoke-induced pulmonary inflammation. Mice received a recombinant adenovirus encoding RelB by intranasal aspiration to induce transient RelB overexpression in the lungs and were subsequently exposed to mainstream cigarette smoke. Markers of inflammation were analyzed after smoke exposure. Neutrophil infiltration, normally increased by smoke exposure, was significantly and potently decreased after RelB overexpression. Cigarette smoke-induced proinflammatory cytokine and chemokine production, cyclooxygenase-2 expression, and prostaglandin E(2) production were also significantly decreased in the context of RelB overexpression. The expression of intercellular adhesion molecule 1, an NF-κB-dependent protein, was decreased, indicating a potential mechanism through which RelB can regulate inflammatory cell migration. Therefore, increased expression and/or activation of RelB could be a novel therapeutic strategy against acute lung inflammation caused by respirable agents and possibly against chronic injury, such as COPD.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: McMillan
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Baglole
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Thatcher
authors.forename: Sanjay
authors.initials: S
authors.lastname: Maggirwar
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sime
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015316:Genetic Therapy; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D012907:Smoking / Q000009:adverse effects*; D051841:Transcription Factor RelB / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D051841:Transcription Factor RelB; D051546:Cyclooxygenase 2; D015232:Dinoprostone