scholarly journals IL-17-Mediated Inflammation Promotes Cigarette Smoke-Induced Genomic Instability

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1173
Author(s):  
Chao Cao ◽  
Baoping Tian ◽  
Xinwei Geng ◽  
Hongbin Zhou ◽  
Zhiwei Xu ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Bronchial Epithelium ◽  
Chromosome Breakage ◽  
Pathological Process ◽  
Cigarette Smoke Exposure ◽  
Mouse Lung ◽  
Epithelium Cells

(1) Background: Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process have yet to be elucidated. (2) Methods: In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. (3) Results: Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissues of smokers than in those of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides this, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. (4) Conclusions: These results suggest that cigarette smoke induces genomic instability at least partially through IL-17-mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.

scholarly journals IL-17-mediated inflammation promotes cigarette smoke-induced genomic instability

2021 ◽  
Author(s):  
Chao Cao ◽  
Baoping Tian ◽  
Xinwei Geng ◽  
Hongbin Zhou ◽  
Zhiwei Xu ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Bronchial Epithelium ◽  
Chromosome Breakage ◽  
Pathological Process ◽  
Cigarette Smoke Exposure ◽  
Mouse Lung ◽  
Epithelium Cells

Abstract Background Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process has yet to be elucidated. Methods In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. Results Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissue of smokers than that of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. Conclusions These results suggest that cigarette smoke induces genomic instability at least partially through IL-17 mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.

Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke

2009 ◽  
Vol 296 (3) ◽  
pp. L418-L429 ◽  
Author(s):  
Eleonora Cavarra ◽  
Paolo Fardin ◽  
Silvia Fineschi ◽  
Annamaria Ricciardi ◽  
Giovanna De Cunto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cigarette Smoke ◽  
Gene Clusters ◽  
Early Response ◽  
Cigarette Smoke Exposure ◽  
Mouse Lung ◽  
Individual Response ◽  
Molecular Signaling ◽  
Gene Expression Response ◽  
Real Time Quantitative Pcr

We have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57BL/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, whereas ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype. The three strains of mice were exposed to smoke from three cigarettes per day, 5 days/wk, for 4 wk. Microarray analysis was carried out on total RNA extracted from the lung using the Affymetrix platform. Cigarette smoke modulates several clusters of genes (i.e., proemphysematous, acute phase response, and cell adhesion) in smoke-sensitive DBA/2 or C57BL/6J strains, but the same genes are not altered by smoke in ICR resistant mice. Only a few genes were commonly modulated by smoke in the three strains of mice. This pattern of gene expression suggests that the response to smoke is strain-dependent and may involve different molecular signaling pathways. Real-time quantitative PCR was used to verify the pattern of modulation of selected genes and their potential biological relevance. We conclude that gene expression response to smoke is highly dependent on the mouse genetic background. We speculate that the definition of gene clusters associated, to various degrees, with mouse susceptibility or resistance to smoke may be instrumental in defining the molecular basis of the individual response to smoke-induced lung injury in humans.

scholarly journals Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 739
Author(s):  
Joo-Hoo Park ◽  
Jae-Min Shin ◽  
Hyun-Woo Yang ◽  
Tae Hoon Kim ◽  
Seung Hoon Lee ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Chronic Rhinosinusitis ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Gelatin Zymography ◽  
Cigarette Smoke Extract ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Luciferase Assay ◽  
Cigarette Smoke Exposure ◽  
Ros Production

Cigarette smoke exposure has been shown to be associated with chronic rhinosinusitis and tissue remodeling. The present study aimed to investigate the effects of cigarette smoke extract (CSE) on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in nasal fibroblasts and to determine the underlying molecular mechanisms. Primary nasal fibroblasts from six patients were isolated and cultured. After the exposure of fibroblasts to CSE, the expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by real-time PCR, ELISA, and immunofluorescence staining. The enzymatic activities of MMP-2 and MMP-9 were measured by gelatin zymography. Reactive oxygen species (ROS) production was analyzed using dichloro-dihydro-fluorescein diacetate and Amplex Red assays. PI3K/Akt phosphorylation and NF-κB activation were determined by Western blotting and luciferase assay. CSE significantly increased MMP-2 expression and inhibited TIMP-2 expression but did not affect MMP-9 and TIMP-1 expression. Furthermore, CSE significantly induced ROS production. However, treatment with ROS scavengers, specific PI3K/Akt inhibitors, NF-κB inhibitor, and glucocorticosteroids significantly decreased MMP-2 expression and increased TIMP-2 expression. Our results suggest that steroids inhibit CSE-regulated MMP-2 and TIMP-2 production and activation through the ROS/ PI3K, Akt, and NF-κB signaling pathways in nasal fibroblasts. CSE may contribute to the pathogenesis of chronic rhinosinusitis by regulating MMP-2 and TIMP-2 expression.

scholarly journals Up-Regulation of Endothelin Receptors Induced by Cigarette Smoke — Involvement of MAPK in Vascular and Airway Hyper-Reactivity

2010 ◽  
Vol 10 ◽  
pp. 2157-2166 ◽  
Author(s):  
Yaping Zhang ◽  
Lars Edvinsson ◽  
Cang-Bao Xu
Keyword(s):  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Smoke Exposure ◽  
Mitogen Activated Protein Kinase ◽  
Endothelin Receptors ◽  
Cigarette Smoke Exposure ◽  
Endothelin Receptor ◽  
Airway Diseases ◽  
Mitogen Activated Protein ◽  
Functional Consequences

Cigarette smoke exposure is well known to cause cardiovascular and airway diseases, both of which are leading causes of death and disability in the world. However, the molecular mechanisms that link cigarette smoke to cardiovascular and airway diseases are not fully understood. Vascular and airway hyper-reactivity plays an important role in the pathogenesis of cardiovascular and airway diseases. Recent studies have demonstrated that endothelin receptor up-regulation mediates vascular and airway hyper-reactivity in response to endothelin-1 (ET-1, endothelin receptor agonist) in cardiovascular and airway diseases. In the vasculature and airways, the main functional consequences of up-regulated endothelin receptors by cigarette smoke exposure are enhanced contraction and proliferation of the smooth muscle cells, which subsequently result in abnormal contraction (spasm) and adverse proliferation (remodeling) of the vasculature and airways. The structural alteration by adverse remodeling involves changes in cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. This review focuses on cigarette smoke exposure that induces activation of intracellular mitogen-activated protein kinase (MAPK) and subsequently results in the up-regulation of endothelin receptors in the vasculature and airways, which mediates vascular and airway hyper-reactivity, one of the important pathogenic characteristics of cardiovascular and airway diseases. Understanding the molecular mechanisms of how cigarette smoke causes up-regulation of endothelin receptors in the vasculature and airways may provide new strategies for the treatment of cigarette smoke—associated cardiovascular and lung diseases.

scholarly journals How the Other Half Lives: What p53 Does When It Is Not Being a Transcription Factor

2019 ◽  
Vol 21 (1) ◽  
pp. 13 ◽  
Author(s):  
Teresa Ho ◽  
Ban Xiong Tan ◽  
David Lane
Keyword(s):  
Cell Death ◽  
Transcription Factor ◽  
Genomic Instability ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Context Dependency ◽  
The Other ◽  
Independent Functions ◽  
Shed Light

It has been four decades since the discovery of p53, the designated ‘Guardian of the Genome’. P53 is primarily known as a master transcription factor and critical tumor suppressor, with countless studies detailing the mechanisms by which it regulates a host of gene targets and their consequent signaling pathways. However, transcription-independent functions of p53 also strongly define its tumor-suppressive capabilities and recent findings shed light on the molecular mechanisms hinted at by earlier efforts. This review highlights the transcription-independent mechanisms by which p53 influences the cellular response to genomic instability (in the form of replication stress, centrosome homeostasis, and transposition) and cell death. We also pinpoint areas for further investigation in order to better understand the context dependency of p53 transcription-independent functions and how these are perturbed when TP53 is mutated in human cancer.

Investigating epithelial plasticity following cigarette smoke exposure in primary human bronchial epithelium

2018 ◽  
Author(s):  
Kristine Nishida ◽  
Si Chen ◽  
Jennifer Nguyen ◽  
Allison Keller ◽  
Vanshika Agarwal ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Bronchial Epithelium ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure ◽  
Epithelial Plasticity

scholarly journals Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium

2010 ◽  
Vol 41 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoling Zhang ◽  
Paola Sebastiani ◽  
Gang Liu ◽  
Frank Schembri ◽  
Xiaohui Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Tract ◽  
Cigarette Smoke ◽  
Expression Profiles ◽  
Physiological Responses ◽  
Bronchial Epithelium ◽  
Nasal Epithelium ◽  
Cigarette Smoke Exposure ◽  
Related Gene ◽  
Gene Expression Response

Previous studies have shown that physiological responses to cigarette smoke can be detected via bronchial airway epithelium gene expression profiling and that heterogeneity in this gene expression response to smoking is associated with lung cancer. In this study, we sought to determine the similarity of the effects of tobacco smoke throughout the respiratory tract by determining patterns of smoking-related gene expression in paired nasal and bronchial epithelial brushings collected from 14 healthy nonsmokers and 13 healthy current smokers. Using whole genome expression arrays, we identified 119 genes whose expression was affected by smoking similarly in both bronchial and nasal epithelium, including genes related to detoxification, oxidative stress, and wound healing. While the vast majority of smoking-related gene expression changes occur in both bronchial and nasal epithelium, we also identified 27 genes whose expression was affected by smoking more dramatically in bronchial epithelium than nasal epithelium. Both common and site-specific smoking-related gene expression profiles were validated using independent microarray datasets. Differential expression of select genes was also confirmed by RT-PCR. That smoking induces largely similar gene expression changes in both nasal and bronchial epithelium suggests that the consequences of cigarette smoke exposure can be measured in tissues throughout the respiratory tract. Our findings suggest that nasal epithelial gene expression may serve as a relatively noninvasive surrogate to measure physiological responses to cigarette smoke and/or other inhaled exposures in large-scale epidemiological studies.

scholarly journals Smoking and the Pathophysiology of Peripheral Artery Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Weiming Wang ◽  
Tingting Zhao ◽  
Kang Geng ◽  
Gang Yuan ◽  
Yue Chen ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Vascular Diseases ◽  
Pathological Process ◽  
Peripheral Artery ◽  
Cell Remodeling ◽  
Artery Disease

Smoking is one of the most important preventable factors causing peripheral artery disease (PAD). The purpose of this review is to comprehensively analyze and summarize the pathogenesis and clinical characteristics of smoking in PAD based on existing clinical, in vivo, and in vitro studies. Extensive searches and literature reviews have shown that a large amount of data exists on the pathological process underlying the effects of cigarette smoke and its components on PAD through various mechanisms. Cigarette smoke extracts (CSE) induce endothelial cell dysfunction, smooth muscle cell remodeling and macrophage phenotypic transformation through multiple molecular mechanisms. These pathological changes are the molecular basis for the occurrence and development of peripheral vascular diseases. With few discussions on the topic, we will summarize recent insights into the effect of smoking on regulating PAD through multiple pathways and its possible pathogenic mechanism.

scholarly journals Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability

2021 ◽  
Vol 9 ◽  
Author(s):  
Rafaela Fagundes ◽  
Leonardo K. Teixeira
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Genomic Instability ◽  
Genome Stability ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Cyclin E ◽  
Replication Stress ◽  
Cyclin E1 ◽  
Cdk2 Complex

DNA replication must be precisely controlled in order to maintain genome stability. Transition through cell cycle phases is regulated by a family of Cyclin-Dependent Kinases (CDKs) in association with respective cyclin regulatory subunits. In normal cell cycles, E-type cyclins (Cyclin E1 and Cyclin E2, CCNE1 and CCNE2 genes) associate with CDK2 to promote G1/S transition. Cyclin E/CDK2 complex mostly controls cell cycle progression and DNA replication through phosphorylation of specific substrates. Oncogenic activation of Cyclin E/CDK2 complex impairs normal DNA replication, causing replication stress and DNA damage. As a consequence, Cyclin E/CDK2-induced replication stress leads to genomic instability and contributes to human carcinogenesis. In this review, we focus on the main functions of Cyclin E/CDK2 complex in normal DNA replication and the molecular mechanisms by which oncogenic activation of Cyclin E/CDK2 causes replication stress and genomic instability in human cancer.

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