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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

Lung APCs of nCB-challenged mice secrete Th17 cell-specific pro-inflammatory cytokines and chemokines.Concentration of pro-inflammatory cytokines and chemokines detected by Multiplex system in the supernatant of overnight cultured of lung CD11c+ cells isolated from indicated groups.*p < 0.05 as determined by the Student's t-test. n = 3 per group. Data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.012
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fig3s2: Lung APCs of nCB-challenged mice secrete Th17 cell-specific pro-inflammatory cytokines and chemokines.Concentration of pro-inflammatory cytokines and chemokines detected by Multiplex system in the supernatant of overnight cultured of lung CD11c+ cells isolated from indicated groups.*p < 0.05 as determined by the Student's t-test. n = 3 per group. Data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.012

Mentions: We previously determined that cigarette smoke induces lung APC activation in human patients and mice, which then induces Th17 cell differentiation in naive T cells (Shan et al., 2009). To determine whether nCB specifically induces Th17 responses in vivo, we first examined lung mDCs from nCB intranasal-challenged mice. Lung CD11c+CD11bhi mDCs were significantly increased in the lungs of nCB-challenged mice when compared with controls (Figure 3A,B). nCB also selectively induced lung Th17 but not Th1 responses relative to control animals (Figure 3C,D and Figure 3—figure supplement 1). Lung CD11c+ APCs isolated from nCB-challenged mice secreted significantly more of the Th17 cell growth factors IL-6 and IL-1β, along with other pro-inflammatory cytokines and chemokines, but not IL-12 or IL-4 (IL-4 was undetectable in both PBS and nCB groups), which promote Th1 and Th2 cell differentiation, respectively (Figure 3—figure supplement 2). To determine if lung APCs from nCB-challenged mice induce specific T cell differentiation programs in vitro, we co-cultured naive splenic CD4+ T cells with CD11c+ cells isolated from lungs of nCB- or PBS-challenged mice. Lung APCs from nCB-challenged mice induced significantly more IL-17A, but neither IFN-γ nor IL-4 production, when compared to controls (Figure 3—figure supplement 3). Lung Th17 responses persisted for at least 7 months following the last nCB challenge (Figure 3—figure supplement 4). Further, Il-17a−/− mice were resistant to nCB challenge as assessed by their attenuated increases in lung volume, lung immune cell infiltration, and the reduced destruction of alveoli (Figure 3E–H) when compared to identically treated WT mice. Thus, in vivo nCB selectively induces chronic lung Th17 responses, which are crucial for CB-induced emphysema in mice.10.7554/eLife.09623.010Figure 3.nCB promotes Th17 responses.


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)

Lung APCs of nCB-challenged mice secrete Th17 cell-specific pro-inflammatory cytokines and chemokines.Concentration of pro-inflammatory cytokines and chemokines detected by Multiplex system in the supernatant of overnight cultured of lung CD11c+ cells isolated from indicated groups.*p < 0.05 as determined by the Student's t-test. n = 3 per group. Data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.012
© Copyright Policy
Related In: Results  -  Collection

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

fig3s2: Lung APCs of nCB-challenged mice secrete Th17 cell-specific pro-inflammatory cytokines and chemokines.Concentration of pro-inflammatory cytokines and chemokines detected by Multiplex system in the supernatant of overnight cultured of lung CD11c+ cells isolated from indicated groups.*p < 0.05 as determined by the Student's t-test. n = 3 per group. Data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.012
Mentions: We previously determined that cigarette smoke induces lung APC activation in human patients and mice, which then induces Th17 cell differentiation in naive T cells (Shan et al., 2009). To determine whether nCB specifically induces Th17 responses in vivo, we first examined lung mDCs from nCB intranasal-challenged mice. Lung CD11c+CD11bhi mDCs were significantly increased in the lungs of nCB-challenged mice when compared with controls (Figure 3A,B). nCB also selectively induced lung Th17 but not Th1 responses relative to control animals (Figure 3C,D and Figure 3—figure supplement 1). Lung CD11c+ APCs isolated from nCB-challenged mice secreted significantly more of the Th17 cell growth factors IL-6 and IL-1β, along with other pro-inflammatory cytokines and chemokines, but not IL-12 or IL-4 (IL-4 was undetectable in both PBS and nCB groups), which promote Th1 and Th2 cell differentiation, respectively (Figure 3—figure supplement 2). To determine if lung APCs from nCB-challenged mice induce specific T cell differentiation programs in vitro, we co-cultured naive splenic CD4+ T cells with CD11c+ cells isolated from lungs of nCB- or PBS-challenged mice. Lung APCs from nCB-challenged mice induced significantly more IL-17A, but neither IFN-γ nor IL-4 production, when compared to controls (Figure 3—figure supplement 3). Lung Th17 responses persisted for at least 7 months following the last nCB challenge (Figure 3—figure supplement 4). Further, Il-17a−/− mice were resistant to nCB challenge as assessed by their attenuated increases in lung volume, lung immune cell infiltration, and the reduced destruction of alveoli (Figure 3E–H) when compared to identically treated WT mice. Thus, in vivo nCB selectively induces chronic lung Th17 responses, which are crucial for CB-induced emphysema in mice.10.7554/eLife.09623.010Figure 3.nCB promotes Th17 responses.

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