Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema

  1. Ran You
  2. Wen Lu
  3. Ming Shan
  4. Jacob M Berlin
  5. Errol LG Samuel
  6. Daniela C Marcano
  7. Zhengzong Sun
  8. William KA Sikkema
  9. Xiaoyi Yuan
  10. Lizhen Song
  11. Amanda Y Hendrix
  12. James M Tour
  13. David Corry
  14. Farrah Kheradmand  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. City of Hope National Medical Center, United States
  3. Rice University, United States

Abstract

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. Here we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema, and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

Article and author information

Author details

  1. Ran You

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Wen Lu

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ming Shan

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jacob M Berlin

    Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Errol LG Samuel

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniela C Marcano

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Zhengzong Sun

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. William KA Sikkema

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Xiaoyi Yuan

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Lizhen Song

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Amanda Y Hendrix

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. James M Tour

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. David Corry

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Farrah Kheradmand

    Department of Medicine, Baylor College of Medicine, Houston, United States
    For correspondence
    farrahk@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Feng Shao, National Institute of Biological Sciences, China

Ethics

Animal experimentation: C57BL/6J mice were purchased from the Jackson Laboratory. ASC-/- mice (C57BL/6 background) were obtained from Dr. Vishva Dixit (Genentech, South San Francisco, CA). IL-17A-/- mice (C57BL/6 background) were obtained from Dr. Chen Dong (The University of Texas MD Anderson Cancer Center, Houston, TX). All mice were bred in the transgenic animal facility at Baylor College of Medicine. All experimental protocols(AN-4589) used in this study were approved by the Institutional Animal Care and Use Committee of Baylor College of Medicine and followed the National Research Council Guide for the Care and Use of Laboratory Animals.

Version history

  1. Received: June 23, 2015
  2. Accepted: September 15, 2015
  3. Accepted Manuscript published: October 5, 2015 (version 1)
  4. Version of Record published: October 21, 2015 (version 2)

Copyright

© 2015, You et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ran You
  2. Wen Lu
  3. Ming Shan
  4. Jacob M Berlin
  5. Errol LG Samuel
  6. Daniela C Marcano
  7. Zhengzong Sun
  8. William KA Sikkema
  9. Xiaoyi Yuan
  10. Lizhen Song
  11. Amanda Y Hendrix
  12. James M Tour
  13. David Corry
  14. Farrah Kheradmand
(2015)
Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema
eLife 4:e09623.
https://doi.org/10.7554/eLife.09623

Share this article

https://doi.org/10.7554/eLife.09623

Further reading

  1. The elemental carbon in cigarette smoke causes inflammation and emphysema in the lung.

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    2. Immunology and Inflammation
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    Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of ‘predictive, preventive, and personalized’ periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes S100A9 and S100A12, located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly.