ArticlePloS one2014
Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Insights into Pharmacological Activities of Nicotine and 6-Hydroxy-L-nicotine, a Bacterial Nicotine Derivative: A Systematic Review.Biomolecules · 2023Pooled it
- Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation.The journal of allergy and clinical immunology. In practice · 2019Trial
- Association Between Serum Growth Factors and Risk of Acute Exacerbation in Chronic Obstructive Pulmonary Disease: A One-Year Prospective Study.International journal of molecular sciences · 2025Article
- Nicotinic receptors in airway disease.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- The controversial effect of smoking and nicotine in SARS-CoV-2 infection.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Review
- Airway Smooth Muscle Regulated by Oxidative Stress in COPD.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- MicroRNA-98 reduces nerve growth factor expression in nicotine-induced airway remodeling.The Journal of biological chemistry · 2020Article
- UPR modulation of host immunity by Pseudomonas aeruginosa in cystic fibrosis.Clinical science (London, England : 1979) · 2020Article
- Age-Associated Tooth Loss and Oral Microbial Dysbiosis in a Mouse Genetic Model of Chronic Nicotine Exposure.Frontiers in immunology · 2020Article
- The Role of the Nuclear Factor-κB Transcriptional Complex in Cortical Immune Activation in Schizophrenia.Biological psychiatry · 2019Article
- Molecular Tension Probes to Investigate the Mechanopharmacology of Single Cells: A Step toward Personalized Mechanomedicine.Advanced healthcare materials · 2018Article
- Nicotine Modulates Cognitive Function inFrontiers in aging neuroscience · 2018Article
- Nicotinic alpha 7 receptor expression and modulation of the lung epithelial response to lipopolysaccharide.PloS one · 2017Article
- Transcriptome sequencing reveals e-cigarette vapor and mainstream-smoke from tobacco cigarettes activate different gene expression profiles in human bronchial epithelial cells.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAirway hyperresponsiveness (AHR) is classically found in asthma, and persistent AHR is associated with poor asthma control. Although airway smooth muscle (ASM) cells play a critical pathophysiologic role in AHR, the paracrine contributions of surrounding cells such as fibroblasts to the contractile phenotype of ASM cells have not been examined fully. This study addresses the hypothesis that nicotine promotes a contractile ASM cell phenotype by stimulating fibroblasts to increase nerve growth factor (NGF) secretion into the environment.
methodsPrimary lung fibroblasts isolated from wild type and α7 nicotinic acetylcholine receptor (α7 nAChR) deficient mice were treated with nicotine (50 µg/ml) in vitro for 72 hours. NGF levels were measured in culture media and in bronchoalveolar lavage (BAL) fluid from asthmatic, smoking and non-smoking subjects by ELISA. The role of the NFκB pathway in nicotine-induced NGF expression was investigated by measuring NFκB nuclear translocation, transcriptional activity, chromatin immunoprecipitation assays, and si-p65 NFκB knockdown. The ability of nicotine to stimulate a fibroblast-mediated, contractile ASM cell phenotype was confirmed by examining expression of contractile proteins in ASM cells cultured with fibroblast-conditioned media or BAL fluid.
resultsNGF levels were elevated in the bronchoalveolar lavage fluid of nicotine-exposed mice, current smokers, and asthmatic children. Nicotine increased NGF secretion in lung fibroblasts in vitro in a dose-dependent manner and stimulated NFκB nuclear translocation, p65 binding to the NGF promoter, and NFκB transcriptional activity. These responses were attenuated in α7 nAChR deficient fibroblasts and in wild type fibroblasts following NFκB inhibition. Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells.
conclusionNicotine stimulates NGF release by lung fibroblasts through α7 nAChR and NFκB dependent pathways. These novel findings suggest that the nicotine-α7 nAChR-NFκB- NGF axis may provide novel therapeutic targets to attenuate tobacco smoke-induced AHR.
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