ArticleExperimental & molecular medicine2018
Cigarette smoke extract enhances neutrophil elastase-induced IL-8 production via proteinase-activated receptor-2 upregulation in human bronchial epithelial cells.
Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell communication and signaling : CCS · 2023Pooled it
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- Chronic Cigarette Smoke Extract Exposure Promotes Genomic and Phenotypic Reprogramming in Lung Cancer Cells.Thoracic cancer · 2026Article
- Cigarette Smoke Extract Alters the Inflammatory Secretome of Osteoarthritis-Affected Synovium Increasing Joint Tissue Oxidative Stress in an Indirect Co-Culture Model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Ashes to Rashes: An Exploration of the Intersection Between Smoking and Cutaneous Lupus Erythematosus.Biomolecules · 2025Review
- Long-Term Cigarette Smoke Exposure Promotes Neutrophil Ferroptosis Resistance, Inducing Neutrophil Extracellular Trap Formation and Driving Glucocorticoid Resistance in Chronic Obstructive Pulmonary Disease.Research (Washington, D.C.) · 2025Article
- The Punicalagin Compound Mitigates Bronchial Epithelial Cell Senescence Induced by Cigarette Smoke Extract through the PAR2/mTOR Pathway.Current medicinal chemistry · 2025Article
- Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-β.International journal of chronic obstructive pulmonary disease · 2024Article
- Molecular Mechanisms and the Interplay of Important Chronic Obstructive Pulmonary Disease Biomarkers Reveals Novel Therapeutic Targets.ACS omega · 2023Review
- Synergistic Detrimental Effects of Cigarette Smoke, Alcohol, and SARS-CoV-2 in COPD Bronchial Epithelial Cells.Pathogens (Basel, Switzerland) · 2023Article
- The role of neutrophil elastase in aortic valve calcification.Journal of translational medicine · 2022Article
- Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract.International journal of molecular sciences · 2022Review
- Article
- Therapeutic Potential of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Recovering From Murine Pulmonary Emphysema Under Cigarette Smoke Exposure.Frontiers in medicine · 2021Article
- Pistacia weinmannifolia ameliorates cigarette smoke and lipopolysaccharide‑induced pulmonary inflammation by inhibiting interleukin‑8 production and NF‑κB activation.International journal of molecular medicine · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although inflammation, oxidative stress, and protease-antiprotease imbalance have been referred to as a pathogenic triad in chronic obstructive pulmonary disease (COPD), little is known about how they interact. The objectives of this study were to elucidate the effect of cigarette smoke extract (CSE) on the neutrophil elastase (NE)-induced inflammatory response and its molecular mechanism in bronchial epithelial cells. We observed that NE activated extracellular signal-regulated kinase (ERK) and induced IL-8 production. Blocking ERK activation using a MEK inhibitor (U0126) suppressed NE-induced IL-8 secretion and knockdown of proteinase-activated receptor 2 (PAR2) using siRNAs inhibited both NE-induced ERK activation and subsequent IL-8 release, suggesting that NE-induced IL-8 production is dependent on PAR2-mediated ERK activation. Interestingly, pre-exposure to CSE markedly enhanced NE-induced IL-8 production. As PAR2 acts as a receptor for NE, we next investigated the effect of CSE on PAR2 expression as a molecular mechanism for the increased IL-8 production induced by NE in CSE exposed cells. CSE, but not NE, increased the expression of PAR2 mRNA and surface membrane protein. Inhibition of p38 MAPK reduced PAR2 expression induced by CSE while inhibition of the ERK and Akt pathway had no effect. Consequently, p38 inhibition significantly abrogated CSE-induced enhancement of IL-8 production in NE-treated cells. Of note, we observed increased PAR2 levels in lung homogenates and lung epithelial cells from CSE-treated mice and from both smokers and patients with COPD. Taken together, these results suggest that CSE upregulates PAR2 in normal human bronchial epithelial cells, thereby enhancing the inflammatory response to NE.
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