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Comparative Study
. 2018 Mar 23:13:989-1000.
doi: 10.2147/COPD.S157728. eCollection 2018.

The effect of electronic cigarette and tobacco smoke exposure on COPD bronchial epithelial cell inflammatory responses

Andrew Higham  1   2 , Declan Bostock  1 , George Booth  2 , Josiah V Dungwa  2 , Dave Singh  1   2
Affiliations
Comparative Study

The effect of electronic cigarette and tobacco smoke exposure on COPD bronchial epithelial cell inflammatory responses

Andrew Higham et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: Electronic cigarettes (e-cigs) are used to help smoking cessation. However, these devices contain harmful chemicals, and there are safety concerns. We have investigated the effects of e-cigs on the inflammatory response and viability of COPD bronchial epithelial cells (BECs).

Methods: BECs from COPD patients and controls were exposed to e-cig vapor extract (ECVE) and the levels of interleukin (IL)-6, C-X-C motif ligand 8 (CXCL8), and lactate dehydrogenase release were measured. We also examined the effect of ECVE pretreatment on polyinosinic:polycytidylic acid (poly I:C)-stimulated cytokine release from BECs. Parallel experiments using Calu-3 cells were performed. Comparisons were made with cigarette smoke extract (CSE).

Results: ECVE and CSE caused an increase in the release of IL-6 and CXCL8 from Calu-3 cells. ECVE only caused toxicity in BECs and Calu-3 cells. Furthermore, ECVE and CSE dampened poly I:C-stimulated C-X-C motif ligand 10 release from both cell culture models, reaching statistical significance for CSE at an optical density of 0.3.

Conclusion: ECVE caused toxicity and reduced the antiviral response to poly I:C. This raises concerns over the safety of e-cig use.

Keywords: COPD; air; cigarette smoke; e-cigs; epithelial cells; liquid interface.

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Conflict of interest statement

Disclosure DS has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards, and research grants from various pharmaceutical companies including Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, GlaxoSmithKline, Glenmark, Johnson and Johnson, Merck, NAPP, Novartis, Pfizer, Skyepharma, Takeda, Teva, Theravance, and Verona. The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The effect of ECVE and CSE on the toxicity of Calu-3 cells. Calu-3 cells (n=6) were exposed to ECVE (0.01–0.3 OD; A, B) or CSE (0.01–0.3 OD; C, D) for 24 hours before TEER (A, C) and LDH release (B, D) were measured. **Significant difference compared to untreated cells where p<0.01. Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; TEER, transepithelial electrical resistance; LDH, lactate dehydrogenase; OD, optical density.
Figure 1
Figure 1
The effect of ECVE and CSE on the toxicity of Calu-3 cells. Calu-3 cells (n=6) were exposed to ECVE (0.01–0.3 OD; A, B) or CSE (0.01–0.3 OD; C, D) for 24 hours before TEER (A, C) and LDH release (B, D) were measured. **Significant difference compared to untreated cells where p<0.01. Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; TEER, transepithelial electrical resistance; LDH, lactate dehydrogenase; OD, optical density.
Figure 2
Figure 2
The effect of ECVE and CSE on the toxicity of primary BECs. Primary BECs from controls (A, B) and COPD patients (C, D) were exposed to ECVE (0.01–0.3 OD) or CSE (0.1–0.3 OD) for 24 hours before TEER (A, C) and LDH release (B, D) were measured. *, **Significant difference compared to untreated cells where p<0.05 and p<0.01, respectively. Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; TEER, transepithelial electrical resistance; LDH, lactate dehydrogenase; OD, optical density; BECs, bronchial epithelial cells; NS, nonsmoker.
Figure 3
Figure 3
The effect of ECVE on cytokine release from Calu-3 cells. Calu-3 cells (n=6) were exposed to ECVE (0.01–0.3 OD) for 24 hours and apical (A, C) and basolateral (B, D) supernatants were analyzed for IL-6 (A, B) and CXCL8 (C, D). *, **Significant difference compared to untreated cells where p<0.05 and p<0.01, respectively. Abbreviations: ECVE, e-cig vapor extract; OD, optical density; IL, interleukin; CXCL8, C-X-C motif ligand 8.
Figure 4
Figure 4
The effect of CSE on cytokine release from Calu-3 cells. Calu-3 cells (n=6) were exposed to CSE (0.01–0.3 OD) for 24 hours and apical (A, C) and basolateral (B, D) supernatants were analyzed for IL-6 (A, B) and CXCL8 (C, D). **Significant difference compared to untreated cells where p<0.01. Abbreviations: CSE, cigarette smoke extract; OD, optical density; IL, interleukin; CXCL8, C-X-C motif ligand 8.
Figure 4
Figure 4
The effect of CSE on cytokine release from Calu-3 cells. Calu-3 cells (n=6) were exposed to CSE (0.01–0.3 OD) for 24 hours and apical (A, C) and basolateral (B, D) supernatants were analyzed for IL-6 (A, B) and CXCL8 (C, D). **Significant difference compared to untreated cells where p<0.01. Abbreviations: CSE, cigarette smoke extract; OD, optical density; IL, interleukin; CXCL8, C-X-C motif ligand 8.
Figure 5
Figure 5
The effect of ECVE and CSE on cytokine release from primary BECs. Primary BECs from controls (A–D) and COPD patients (E–H) were exposed to ECVE (0.01–0.3 OD) or CSE (0.1–0.3 OD) for 24 hours and apical (A, C, E, G) and basolateral (B, D, F, H) supernatants were analyzed for IL-6 (A, B, E, F) and CXCL8 (C, D, G, H). Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; OD, optical density; BECs, bronchial epithelial cells; IL, interleukin; CXCL8, C-X-C motif ligand 8.
Figure 6
Figure 6
The effect of ECVE on p38 MAPK activation in Calu-3 cells. Calu-3 cells (n=3) were exposed to ECVE (0.1 OD) for 5–240 minutes before cell lysates were analyzed for phosphorylated p38 MAPK (p-p38) by Western blot. p-p38 levels were normalized to the loading control β-actin. *, **, ***Significant difference compared to untreated time-matched control where p<0.05, p<0.01, and p<0.001, respectively. Abbreviations: ECVE, e-cig vapor extract; OD, optical density; MAPK, mitogen-activated protein kinase.
Figure 7
Figure 7
The effect of ECVE and CSE on poly I:C-stimulated cytokine release from Calu-3 cells. Calu-3 cells (n=3) were exposed to ECVE (0.01–0.1 OD) or CSE (0.1–0.3 OD) for 1 hour prior to poly I:C stimulation for 24 hours. Supernatants were analyzed for IL-6 (A), CXCL8 (B), CXCL10 (C), and CCL5 (D). *Significant difference compared to untreated cells where p<0.05. Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; OD, optical density; IL, interleukin; CXCL8, C-X-C motif ligand 8; CXCL10, C-X-C motif ligand 10; CCL5, C-C motif ligand 5; poly I:C, polyinosinic:polycytidylic acid.
Figure 8
Figure 8
The effect of ECVE and CSE on poly I:C-stimulated apical cytokine release from control BECs. Primary BECs from controls were exposed to ECVE (0.01–0.1 OD) or CSE (0.1–0.3 OD) for 1 hour prior to poly I:C stimulation for 24 hours. Supernatants were analyzed for IL-6 (A), CXCL8 (B), CXCL10 (C), and CCL5 (D). *, **Significant difference compared to untreated cells where p<0.05 and p<0.01, respectively. Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; OD, optical density; IL, interleukin; CXCL8, C-X-C motif ligand 8; CXCL10, C-X-C motif ligand 10; CCL5, C-C motif ligand 5; poly I:C, polyinosinic:polycytidylic acid; BECs, bronchial epithelial cells.
Figure 9
Figure 9
The effect of ECVE and CSE on poly I:C-stimulated apical cytokine release from COPD BECs. Primary BECs from COPD patients were exposed to ECVE (0.01–0.1 OD) or CSE (0.1–0.3 OD) for 1 hour prior to poly I:C stimulation for 24 hours. Supernatants were analyzed for IL-6 (A), CXCL8 (B), CXCL10 (C), and CCL5 (D). Abbreviations: ECVE, e-cig vapor extract; CSE, cigarette smoke extract; OD, optical density; IL, interleukin; CXCL8, C-X-C motif ligand 8; CXCL10, C-X-C motif ligand 10; CCL5, C-C motif ligand 5; poly I:C, polyinosinic:polycytidylic acid; BECs, bronchial epithelial cells.
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