Cigarette smoke represses the innate immune response to asbestos

Our plain-English summary of Cigarette smoke represses the innate immune response to asbestos, by G.F. Morris, S. Danchuk, Y. Wang, et al (Physiological Reports, 2015).

The study

• Authors: G.F. Morris, S. Danchuk, Y. Wang, B. Xu, R.J. Rando, A.R. Brody, B. Shan, D.E. Sullivan
• Journal: Physiological Reports
• Published: 2015;3(12)
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

In plain English

This was an experimental study in mice combined with cell-culture work. Wild-type C57BL/6 mice were exposed nose-only to an aerosol of NIEHS medium grade chrysotile asbestos (average 17.1-21.2 mg per cubic metre) for 5 hours one day a week and whole-body to cigarette smoke from KY3R4F reference cigarettes 5 hours a day, four days a week, for five weeks; control mice breathed filtered room air. Bronchoalveolar lavage fluid was analysed. Asbestos raised BAL protein, lactate dehydrogenase, IL-33 (more than sixfold over unexposed), IL-18 (fourfold over unexposed) and active caspase-1. Mice given cigarette smoke plus asbestos had significantly lower IL-33 (about 50 percent lower), IL-18 and active caspase-1 than asbestos-only mice, fewer eosinophils, and smaller lesions at bronchiolar-alveolar duct junctions. HMGB1 and IL-1 beta were about 30 percent lower with coexposure but did not reach significance (P equals 0.058 and 0.056). In THP-1 human monocytic cells, cigarette smoke extract repressed asbestos-induced release of IL-1 beta, caspase-1 and IL-18. The authors concluded that cigarette smoke represses central components of the innate immune response to inhaled asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Controlled animal inhalation experiment in mice with accompanying in vitro human cell-line experiments
• Who was studied: Wild-type C57BL/6 mice aged 8-10 weeks in four exposure groups (for example, in one set of analyses air n=14, CS n=11, asbestos n=17, CS+asbestos n=18), plus the human monocyte cell line THP-1
• Exposure: Inhaled NIEHS medium grade chrysotile asbestos aerosol (average 17.1-21.2 mg/m3, 5 h once weekly for 5 weeks) and/or whole-body cigarette smoke from KY3R4F reference cigarettes (about 150 mg/m3 total suspended particles, 5 h/day, 4 days/week, 5 weeks); in vitro, chrysotile asbestos and cigarette smoke extract
• Main results:
  • In mice, asbestos increased BAL total protein and LDH; cigarette smoke alone had no effect on these injury markers and coexposure had only a small, non-significant effect
  • Asbestos modestly increased BAL neutrophils and eosinophils; adding cigarette smoke did not change neutrophils but repressed the eosinophil increase
  • BAL IL-33 was more than sixfold higher in asbestos-exposed mice than unexposed controls, and cigarette smoke plus asbestos reduced it by about 50 percent
  • BAL HMGB1 was about 30 percent lower in CS+asbestos than asbestos-only mice, but the difference did not reach significance
  • BAL IL-1 beta was repressed about 30 percent by coexposure, statistically insignificant (P = 0.056)
  • Active caspase-1 in BAL fluid was about 1.8-fold higher in asbestos-exposed mice than in CS+asbestos mice
  • BAL IL-18 was fourfold higher in asbestos-exposed mice than unexposed controls, and significantly lower in CS+asbestos mice than in asbestos-only mice
  • Lesions at bronchiolar-alveolar duct junctions were about 40 percent larger in asbestos-exposed than in CS+asbestos-exposed mice (the Results text describes attenuation of about 50 percent)
  • In THP-1 cells, cigarette smoke extract repressed asbestos-induced release of IL-1 beta and caspase-1 without additional cell lysis
  • In THP-1 cells, asbestos increased supernatant IL-18 and cleaved caspase-1 and mature IL-1 beta; adding cigarette smoke extract repressed this induction
• The authors' conclusion: The authors concluded that cigarette smoke represses several well-characterised components of the innate immune response to inhaled asbestos, and postulated this could delay fiber clearance and prolong inflammation
• Limitations the authors state:
  • Whole-body smoke exposure means ingestion of smoke components during grooming could have contributed
  • The experiments were designed to detect lesion development, not resolution; a longer observation period after exposure would be needed
  • The long-term fibroproliferative and cancer outcomes of combined exposure were not established in this model
  • The role of the NLRP3 inflammasome in lung tumorigenesis was not evaluated

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Lung Cancer, Asbestos Exposure, Tumorigenesis, Bronchoalveolar Lavage (BAL).

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