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

You R, Lu W, Shan M, Berlin JM, Samuel EL, Marcano DC, Sun Z, Sikkema WK, Yuan X, Song L, Hendrix AY, Tour JM, Corry DB, Kheradmand F - Elife (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Baylor College of Medicine, Houston, 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. In this study, 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.

No MeSH data available.


Related in: MedlinePlus

Direct effect of nCB on T helper cell differentiation in vitro.(A) Flow cytometric analysis of intracellular cytokine staining of IFN-γ (Th1), IL-17A (Th17), and Foxp3/CD25 surface expression (Tregs). Diff. is the differentiation conditions for Th1, Th17, and Tregs (as described in the methods). Y-axis of both Th1 and Th17 panel is empty channel. (B) Cumulative summary of four independent experiments for Treg differentiation. **p < 0.01 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.09623.015
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fig3s5: Direct effect of nCB on T helper cell differentiation in vitro.(A) Flow cytometric analysis of intracellular cytokine staining of IFN-γ (Th1), IL-17A (Th17), and Foxp3/CD25 surface expression (Tregs). Diff. is the differentiation conditions for Th1, Th17, and Tregs (as described in the methods). Y-axis of both Th1 and Th17 panel is empty channel. (B) Cumulative summary of four independent experiments for Treg differentiation. **p < 0.01 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.09623.015

Mentions: We next explored whether nCB plays a direct role (i.e., independent of APCs) on T helper cell differentiation. To address this question, we polarized T cells toward Th1, Th17, and regulatory (Treg) phenotypes in the presence or absence of nCB in vitro. We found that nCB did not affect Th1 or Th17 cell differentiation directly (Figure 3—figure supplement 5A). However, nCB treatment significantly inhibited Treg differentiation (Figure 3—figure supplement 5A,B). These findings indicate that nCB promotes sterile inflammation by inducing Th17 differentiation indirectly through APCs and directly by inhibiting Treg differentiation.


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

You R, Lu W, Shan M, Berlin JM, Samuel EL, Marcano DC, Sun Z, Sikkema WK, Yuan X, Song L, Hendrix AY, Tour JM, Corry DB, Kheradmand F - Elife (2015)

Direct effect of nCB on T helper cell differentiation in vitro.(A) Flow cytometric analysis of intracellular cytokine staining of IFN-γ (Th1), IL-17A (Th17), and Foxp3/CD25 surface expression (Tregs). Diff. is the differentiation conditions for Th1, Th17, and Tregs (as described in the methods). Y-axis of both Th1 and Th17 panel is empty channel. (B) Cumulative summary of four independent experiments for Treg differentiation. **p < 0.01 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.09623.015
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612775&req=5

fig3s5: Direct effect of nCB on T helper cell differentiation in vitro.(A) Flow cytometric analysis of intracellular cytokine staining of IFN-γ (Th1), IL-17A (Th17), and Foxp3/CD25 surface expression (Tregs). Diff. is the differentiation conditions for Th1, Th17, and Tregs (as described in the methods). Y-axis of both Th1 and Th17 panel is empty channel. (B) Cumulative summary of four independent experiments for Treg differentiation. **p < 0.01 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. Data are mean ± SEM.DOI:http://dx.doi.org/10.7554/eLife.09623.015
Mentions: We next explored whether nCB plays a direct role (i.e., independent of APCs) on T helper cell differentiation. To address this question, we polarized T cells toward Th1, Th17, and regulatory (Treg) phenotypes in the presence or absence of nCB in vitro. We found that nCB did not affect Th1 or Th17 cell differentiation directly (Figure 3—figure supplement 5A). However, nCB treatment significantly inhibited Treg differentiation (Figure 3—figure supplement 5A,B). These findings indicate that nCB promotes sterile inflammation by inducing Th17 differentiation indirectly through APCs and directly by inhibiting Treg differentiation.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Baylor College of Medicine, Houston, 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. In this study, 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.

No MeSH data available.


Related in: MedlinePlus