Oxidative stress‐mediated epidermal growth factor receptor activation by cigarette smoke or heated tobacco aerosol in human primary bronchial epithelial cells from multiple donors

Abstract

The epidermal growth factor receptor (EGFR) signaling pathway has essential roles in maintaining homeostasis of various tissues by regulating cell proliferation and differentiation. Deregulation of the EGFR signaling pathway is associated with various chronic diseases including chronic obstructive pulmonary disease. Cigarette smoke (CS) is known to activate EGFR, which is linked to chronic obstructive pulmonary disease. The biological sequence from CS exposure to EGFR activation is initiated by oxidative stress caused by intracellular reactive oxygen species (ROS) and the depletion of glutathione, which led to EGFR ligand secretion and EGFR activation.We hypothesized that reducing exposure to CS constituents contributes to preventing CS-inducible EGFR activation. Therefore, we examined the aerosol from heated tobacco products (HTPs) because the aerosol contains fewer chemical constituents at lower levels than CS. We exposed primary human bronchial epithelial cells from four donors to the extracts of CS from a 1R6F reference cigarette or HTP aerosol from three in-market products, including our DT3.0a. The biological sequence from ROS to EGFR activation was assessed. CS induced all the tested endpoints although inter-donor differences were observed, whereas HTPs elicited most of the biological events at higher concentrations; however, EGFR phosphorylation was not observed even at fivefold higher concentration than CS. Overall, our results indicate that HTPs are less effective than CS to elicit ROS-induced EGFR activation. The reduced-risk potential of HTPs on EGFR-related diseases should be investigated further. In addition, testing with multiple donors is warranted when considering the individual differences in responses of primary cells to stimuli.

Could cigarette smoke be associated with metaplastic type of meibomian gland dysfunction?

“…2 Furthermore, it has been demonstrated that EGF (Epidermal Growth Factor) is produced in epithelial cells in response to smoke and that further increases the possibility of metaplastic as well as hyperplastic changes. 5 Therefore, we suggest that there exists a strong relation between exposure to cigarette smoke and the development of metaplastic meibomian gland dysfunction. Further studies in this regard might help in prevention, as well as newer diagnostic approaches towards MGD especially in populations exposed to cigarette smoke on a regular basis.…”

The Product Science of Electrically Heated Tobacco Products: An Updated Narrative Review of the Scientific Literature

“…Four articles were identified that utilized fractionated sampling liquid extracts to compare the in vitro effects of HTPs with cigarettes on respiratory tract cell lines [79][80][81][82]. In the first study, the gas-vapor phase of mainstream smoke from three 3R4F Kentucky reference cigarettes and of aerosol from six IQOS HTP consumables was bubbled into PBS to produce extracts [79].…”

Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review

“…ROS were detected in the emissions from them [ 216 , 217 ]. These emissions have the potential to incite ROS production in cells, with NOX and mitochondria acting as cellular sources for ROS [ 218 , 219 , 220 , 221 , 222 ]. However, there appears to be a distinction in the quantitative aspect of their capacity to induce ROS formation.…”

“…In the comparative studies, emissions from HTPs were found to contain a lower quantity of ROS compared to CS [ 79 ], and both HTPs and E-cigarettes demonstrated a lower ability to stimulate cells to produce ROS compared to conventional cigarettes [ 220 , 223 , 224 , 225 , 226 ]. Nevertheless, E-cigarettes induced a comparable alteration in oxidative stress makers to CS in mice studies [ 227 ].…”