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.

Asbestos, Smoking and Lung Cancer: An Update

“…A very recent study in a mouse inhalation model shows that exposure to combined tobacco smoke and chrysotile asbestos suppressed the innate immune response (NLRP3 inflammasome) to asbestos fibers, resulting in reduced fiber clearance and more chronic inflammation, leading to carcinogenesis. Confirmatory in vitro studies in human monocytes produced a similar effect with combined tobacco smoke and asbestos exposure [98].…”

The inflammasomes, immune guardians at defence barriers

“…Indeed, IL‐1 β has been shown to be a marker of COPD severity as individuals with COPD present higher levels of IL‐1 β in serum . In contrast, another study shows that cigarette smoke reduces the inflammatory response in mice treated with another NLRP3‐activating crystal: asbestos . Although contradictory, the reduction of the inflammatory response could be explained by the promotion of the proteasomal degradation of NLRP3 mediated by its ubiquitination …”

E-cigarette vapour from base components propylene glycol and vegetable glycerine inhibits the inflammatory response in macrophages and epithelial cells

“…Nigericin is a NLRP3 inflammasome inducer and the NLRP3 inflammasome is most likely to be involved in inhaled airway challenges such as E-vapour. While inhibition of inflammasome activation by basic E-vapour has not been reported before, NLRP3 inflammasome inhibition by cigarette smoke has been described (Morris., 2015; Han., 2017; Ye., 2019); NLRP3 protein was reduced via ubiquitin mediated proteasomal processing in THP1 cells and C57BL/6 mice exposed to cigarettes smoke, and the NLRP3 inflammasome was supressed in reaction to Candida albicans in a rat model exposed to cigarette smoke. Indeed, Morris et al showed the NLRP3 inflammasomes response to asbestos was inhibited by cigarettes smoke, while we show here that nigericin fails to activate primed macrophages in the presence of basic E-vapour.…”