title: Cigarette smoke represses the innate immune response to asbestos.
abstract: Both cigarette smoke (CS) and asbestos cause lung inflammation and lung cancer, and at high asbestos exposure levels, populations exposed to both of these carcinogens display a synergistic increase in the development of lung cancer. The mechanisms through which these two toxic agents interact to promote lung tumorigenesis are poorly understood. Here, we begin to dissect the inflammatory signals induced by asbestos in combination with CS using a rodent inhalation model and in vitro cell culture. Wild-type C57BL/6 mice were exposed to room air as a control, CS, and/or asbestos (4 days per week to CS and 1 day per week to asbestos for 5 weeks). Bronchoalveolar lavage (BAL) fluid was collected following exposure and analyzed for inflammatory mediators. Asbestos-exposed mice displayed an increased innate immune response consistent with NLRP3 inflammasome activation. Compared to mice exposed only to asbestos, animals coexposed to CS + asbestos displayed attenuated levels of innate immune mediators and altered inflammatory cell recruitment. Histopathological changes in CS + asbestos-exposed mice correlated with attenuated fibroproliferative lesion development relative to their counterparts exposed only to asbestos. In vitro experiments using a human monocyte cell line (THP-1 cells) supported the in vivo results in that coexposure to cigarette smoke extract repressed NLRP3 inflammasome markers in cells treated with asbestos. These observations indicate that CS represses central components of the innate immune response to inhaled asbestos.
authors.affiliation: Departments of Pathology and Laboratory Medicine, Program in Lung Biology, New Orleans, Louisiana gmorris2@tulane.edu.
authors.forename: Gilbert F
authors.initials: GF
authors.lastname: Morris
authors.affiliation: Microbiology and Immunology, Program in Lung Biology, New Orleans, Louisiana.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Danchuk
authors.affiliation: Departments of Pathology and Laboratory Medicine, Program in Lung Biology, New Orleans, Louisiana.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Departments of Pathology and Laboratory Medicine, Program in Lung Biology, New Orleans, Louisiana.
authors.forename: Beibei
authors.initials: B
authors.lastname: Xu
authors.affiliation: Global Environmental Health Sciences, Tulane University Health Sciences Center Program in Lung Biology, New Orleans, Louisiana.
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Rando
authors.affiliation: Departments of Pathology and Laboratory Medicine, Program in Lung Biology, New Orleans, Louisiana.
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Brody
authors.affiliation: College of Medical Sciences, Washington State University Spokane Program in Lung Biology, Spokane, Washington.
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.affiliation: Microbiology and Immunology, Program in Lung Biology, New Orleans, Louisiana.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Sullivan
keywords: Asbestos; IL‐18; IL‐1β; NLRP3 inflammasome; cigarette smoke