Comparative oxidative and inflammatory responses to heated tobacco aerosol and cigarette smoke extracts in human lung fibroblasts.
8 affiliations
- 1Doctoral Program in Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia.
- 2Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia.
- 3Department of Physiology, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
- 4Physiology Molecular Laboratory, Biological Activity Division, Central Laboratory, Universitas Padjadjaran, Bandung, Indonesia.
- 5Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia.
- 6Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
- 7Center of Excellence for the Acceleration of Harm Reduction (CoEHAR), University of Catania, Catania, Italy.
- 8Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Abstract
Introduction
Combustible cigarette smoke induces oxidative stress and inflammation in lung cells. Heated tobacco products (HTPs) have been proposed as alternatives with reduced toxicant emissions, but their cellular effects remain incompletely characterized.Methods
MRC-5 human lung fibroblasts were exposed to aqueous cigarette smoke extract (CSE; 0.1-1.0 puffs/mL) or heated tobacco aerosol extract (HTE; 1.5-5.5 puffs/mL for viability, 3.0-5.5 puffs/mL for other endpoints). Concentrations were anchored to each product's 24 h IC₅₀ (CSE 0.70 puffs/mL, 95% CI 0.63-0.77; HTE 4.76 puffs/mL, 95% CI 4.39-5.16). Cytotoxicity, oxidation-sensitive dihydroethidium (DHE) fluorescence, intracellular TNF-α and IL-6, and morphology were assessed. ATG5 protein was included as an exploratory endpoint.Results
Both extracts increased DHE fluorescence and intracellular TNF-α and IL-6 in a concentration-dependent manner, with reduced viability and morphological changes. ATG5 findings were inconclusive, as no concentration differed from the untreated control. Nominal puff concentrations were not considered equivalent doses. In an exploratory comparison near each product's 24 h IC₅₀ (CSE 0.7 and HTE 4.75 puffs/mL), CSE produced greater DHE fluorescence (3.17- versus 2.31-fold over vehicle) and greater intracellular IL-6 and TNF-α signals than HTE. Equivalent viability at the 90 min and 4 h endpoints was not established.Discussion
Under these study-specific conditions, HTE elicited quantitatively smaller oxidative and inflammatory responses than CSE at the selected comparison concentrations.
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BibTeX
@article{abelia2026comparative,
title = {{Comparative oxidative and inflammatory responses to heated tobacco aerosol and cigarette smoke extracts in human lung fibroblasts.}},
author = {Xylia Annisa Abelia and Ronny Lesmana and Melisa Intan Barliana and Massimo Caruso and Riccardo Polosa},
journal = {Frontiers in physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1902675},
url = {https://europepmc.org/article/MED/43010954},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparative oxidative and inflammatory responses to heated tobacco aerosol and cigarette smoke extracts in human lung fibroblasts.
AU - Xylia Annisa Abelia
AU - Ronny Lesmana
AU - Melisa Intan Barliana
AU - Massimo Caruso
AU - Riccardo Polosa
PY - 2026
DA - 2026/10/27
JO - Frontiers in physiology
DO - 10.3389/fphys.2026.1902675
UR - https://europepmc.org/article/MED/43010954
AB - Introduction Combustible cigarette smoke induces oxidative stress and inflammation in lung cells. Heated tobacco products (HTPs) have been proposed as alternatives with reduced toxicant emissions, but their cellular effects remain incompletely characterized.Methods MRC-5 human lung fibroblasts were exposed to aqueous cigarette smoke extract (CSE; 0.1-1.0 puffs/mL) or heated tobacco aerosol extract (HTE; 1.5-5.5 puffs/mL for viability, 3.0-5.5 puffs/mL for other endpoints). Concentrations were anchored to each product's 24 h IC₅₀ (CSE 0.70 puffs/mL, 95% CI 0.63-0.77; HTE 4.76 puffs/mL, 95% CI 4.39-5.16). Cytotoxicity, oxidation-sensitive dihydroethidium (DHE) fluorescence, intracellular TNF-α and IL-6, and morphology were assessed. ATG5 protein was included as an exploratory endpoint.Results Both extracts increased DHE fluorescence and intracellular TNF-α and IL-6 in a concentration-dependent manner, with reduced viability and morphological changes. ATG5 findings were inconclusive, as no concentration differed from the untreated control. Nominal puff concentrations were not considered equivalent doses. In an exploratory comparison near each product's 24 h IC₅₀ (CSE 0.7 and HTE 4.75 puffs/mL), CSE produced greater DHE fluorescence (3.17- versus 2.31-fold over vehicle) and greater intracellular IL-6 and TNF-α signals than HTE. Equivalent viability at the 90 min and 4 h endpoints was not established.Discussion Under these study-specific conditions, HTE elicited quantitatively smaller oxidative and inflammatory responses than CSE at the selected comparison concentrations.
SN - 1664-042X
ER -