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.

Cigarette smoke extract amplifies NADPH oxidase-dependent ROS production to inactivate PTEN by oxidation in BEAS-2B cells

2021 ◽  
Vol 150 ◽  
pp. 112050
Author(s):  
Bangrong Cai ◽  
Mengya Liu ◽  
Jinxing Li ◽  
Dujuan Xu ◽  
Jiansheng Li
Keyword(s):  
Nadph Oxidase ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
Ros Production

scholarly journals Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Garrett Pehote ◽  
Manish Bodas ◽  
Kathryn Brucia ◽  
Neeraj Vij
Keyword(s):  
Cigarette Smoke ◽  
Therapeutic Potential ◽  
Underlying Mechanism ◽  
Cigarette Smoke Extract ◽  
Cigarette Smoke Exposure ◽  
Control Group ◽  
Bacterial Clearance ◽  
Bacterial Killing ◽  
Bactericidal Activities ◽  
Autophagy Inhibition

Introduction. Cigarette smoke (CS) exposure is the leading risk factor for COPD-emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity. However, the underlying mechanism is unclear. Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells) and Pseudomonas aeruginosa (PA01-GFP) as an experimental model. Methods. Briefly, RAW cells were treated with cigarette smoke extract (CSE), chloroquine (autophagy inhibitor), TFEB-shRNA, CFTR(inh)-172, and/or fisetin prior to bacterial infection for functional analysis. Results. Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p<0.01), autophagy inhibition (p<0.05; p<0.01), TFEB knockdown (p<0.01; p<0.001), and inhibition of CFTR function (p<0.001; p<0.01) in comparison to the control group(s) that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p<0.05; p<0.01; and p<0.001). Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p<0.01; p<0.001), which warrants further investigation. Conclusions. Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis.

Differential induction of apoptosis by cigarette smoke extract in primary human lung fibroblast strains: implications for emphysema

2006 ◽  
Vol 291 (1) ◽  
pp. L19-L29 ◽  
Author(s):  
Carolyn J. Baglole ◽  
Seth M. Bushinsky ◽  
Tatiana M. Garcia ◽  
Aruna Kode ◽  
Irfan Rahman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Cigarette Smoke ◽  
Tobacco Smoke ◽  
Mitochondrial Membrane ◽  
Human Lung ◽  
Cigarette Smoke Extract ◽  
Lung Fibroblast ◽  
Cigarette Smoke Exposure ◽  
Human Lung Fibroblast

Cigarette smoke is the principal cause of emphysema. Recent attention has focused on the loss of alveolar fibroblasts in the development of emphysema. Fibroblasts may become damaged by oxidative stress and undergo apoptosis as a result of cigarette smoke exposure. Not all smokers develop lung diseases associated with tobacco smoke, a fact that may reflect individual variation among human fibroblast strains. We hypothesize that fibroblasts from different human beings vary in their ability to undergo apoptosis after cigarette smoke exposure. This could account for emphysematous changes that occur in the lungs of some but not all smokers. Primary human lung fibroblast strains were exposed to cigarette smoke extract (CSE) and assessed for viability, morphological changes, and mitochondrial transmembrane potential as indicators of apoptosis. We also examined the generation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-nonenal, and changes in glutathione (GSH) and glutathione disulfide (GSSG) levels. Each human lung fibroblast strain exhibited a differential sensitivity to CSE as judged by changes in mitochondrial membrane potential, viability, ROS generation, and glutathione production. Interestingly, the thiol antioxidants N-acetyl-l-cysteine and GSH eliminated CSE-induced changes in fibroblast morphology such as membrane blebbing, nuclear condensation, and cell size and prevented alterations in mitochondrial membrane potential and the generation of ROS. These findings support the concept that oxidative stress and apoptosis are responsible for fibroblast death associated with exposure to tobacco smoke. Variations in the sensitivity of fibroblasts to cigarette smoke may account for the fact that only some smokers develop emphysema.

Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF-α signaling

2007 ◽  
Vol 292 (1) ◽  
pp. L125-L133 ◽  
Author(s):  
J. L. Wright ◽  
H. Tai ◽  
R. Wang ◽  
X. Wang ◽  
A. Churg
Keyword(s):  
Pulmonary Hypertension ◽  
Matrix Metalloproteinases ◽  
Cigarette Smoke ◽  
Vascular Remodeling ◽  
Smoke Exposure ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Cigarette Smoke Exposure ◽  
Mrna Levels ◽  
Gelatinase Activity ◽  
Tnf Α

Cigarette smoke exposure causes vascular remodeling and pulmonary hypertension by poorly understood mechanisms. To ascertain whether cigarette smoke exposure affects production of matrix metalloproteinases (MMPs) in the pulmonary vessels, we exposed C57Bl/6 (C57) mice or mice lacking TNF-α receptors (TNFRKO) to smoke daily for 2 wk or 6 mo. Using laser capture microdissection and RT-PCR analysis, we examined gene expression of MMP-2, MMP-9, MMP-12, MMP-13, and tissue inhibitor of metalloproteinase (TIMP-1) and examined protein production by immunohistochemistry for MMP-2, MMP-9, and MMP-12 in small intrapulmonary arteries. At 2 wk, mRNA levels of TIMP-1 and all MMPs were increased in the C57, but not TNFRKO, mice, and immunoreactive protein for MMP-2, MMP-9, and MMP-12 was also increased in the C57 mice. Increased gelatinase activity was identified by in situ and bulk tissue zymography. At 6 mo, only MMP-12 mRNA levels remained increased in the C57 mice, but at a much lower level; however, MMP-2 mRNA levels increased in the TNFRKO mice. We conclude that smoke exposure increases MMP production in the small intrapulmonary arteries but that, with the exception of MMP-12, increased MMP production is transient. MMPs probably play a role in smoke-induced vascular remodeling, as they do in other forms of pulmonary hypertension, implying that MMP inhibitors might be beneficial. MMP production is largely TNF-α dependent, further supporting the importance of TNF-α in the pathogenesis of cigarette smoke-induced lung disease.

scholarly journals Ninjinyoeito Ameliorated Cigarette Smoke Extract-induced Apoptosis and Inflammation Through JNK Signaling Inhibition in Human Lung Fibroblasts

2021 ◽  
Author(s):  
Kenta Murata ◽  
Nina Fujita ◽  
Ryuji Takahashi
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Human Lung ◽  
Cigarette Smoke Extract ◽  
Lung Fibroblasts ◽  
Ros Production ◽  
Jnk Signaling ◽  
Human Lung Fibroblasts ◽  
Induced Apoptosis ◽  
Apoptosis And Inflammation

Abstract BackgroundCigarette smoke is a major risk factor for various lung diseases, such as chronic obstructive pulmonary disease (COPD). Ninjinyoeito (NYT), a traditional Chinese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT treatment can ameliorate cigarette smoke-induced lung injury, which is a destructive index in mice; however, the detailed underlying mechanism remains unknown. PurposeThe purpose of this study was to investigate whether NYT ameliorates cigarette smoke-induced lung injury and inflammation in human lung fibroblasts and determine its mechanism of action. MethodsWe prepared a cigarette smoke extract (CSE) from commercially available cigarettes to induce cell injury and inflammation in the human lung fibroblast cell line HFL1. The cells were pretreated with NYT for 24 h prior to CSE exposure. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) cytotoxicity assay and cell counting kit (CCK)-8. IL-8 level in the cell culture medium was measured by performing Enzyme-Linked Immuno Sorbent Assay (ELISA). To clarify the mechanisms of NYT, we used CellROX Green Reagent for reactive oxygen species (ROS) production and western blotting analysis for cell signaling.ResultsExposure of HFL1 cells to CSE for 24 h induced apoptosis and interleukin (IL)-8 release. Pretreatment with NYT inhibited apoptosis and IL-8 release. Furthermore, CSE exposure for 24 h increased the production of ROS and phosphorylation levels of p38 and JNK. Pretreatment with NYT only inhibited CSE-induced JNK phosphorylation, and not ROS production and p38 phosphorylation. These results suggest that NYT acts as a JNK-specific inhibitor.ConclusionNYT treatment ameliorated CSE-induced apoptosis and inflammation by inhibiting the JNK signaling pathway. Finally, these results suggest that NYT may be a promising therapeutic agent for patients with COPD.

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 p19Arf Exacerbates Cigarette Smoke-Induced Pulmonary Dysfunction

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 462
Author(s):  
Ryuta Mikawa ◽  
Tadashi Sato ◽  
Yohei Suzuki ◽  
Hario Baskoro ◽  
Koichiro Kawaguchi ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Cellular Senescence ◽  
Cigarette Smoke Extract ◽  
Senescent Cell ◽  
Cigarette Smoke Exposure ◽  
Pulmonary Dysfunction ◽  
Potential Therapeutic Target ◽  
Tissue Compliance

Senescent cells accumulate in tissues during aging or pathological settings. The semi-genetic or pharmacological targeting of senescent cells revealed that cellular senescence underlies many aspects of the aging-associated phenotype and diseases. We previously reported that cellular senescence contributes to aging- and disease-associated pulmonary dysfunction. We herein report that the elimination of Arf-expressing cells ameliorates cigarette smoke-induced lung pathologies in mice. Cigarette smoke induced the expression of Ink4a and Arf in lung tissue with concomitant increases in lung tissue compliance and alveolar airspace. The elimination of Arf-expressing cells prior to cigarette smoke exposure protected against these changes. Furthermore, the administration of cigarette smoke extract lead to pulmonary dysfunction, which was ameliorated by subsequent senescent cell elimination. Collectively, these results suggest that senescent cells are a potential therapeutic target for cigarette smoking-associated lung disease.

scholarly journals Cigarette Smoke Extract Stimulates Rat Pulmonary Artery Smooth Muscle Cell Proliferation via PKC-PDGFB Signaling

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ai-ping Xing ◽  
Yong-cheng Du ◽  
Xiao-yun Hu ◽  
Jian-ying Xu ◽  
Huan-ping Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Cigarette Smoke ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cigarette Smoke Extract ◽  
Direct Role ◽  
Protein Levels ◽  
Pulmonary Artery Smooth Muscle

Accumulating evidence suggests a direct role for cigarette smoke in pulmonary vascular remodeling, which contributes to the development of pulmonary hypertension. However, the molecular mechanisms underlying this process remain poorly understood. Platelet-derived growth factor (PDGF) is a potential mitogen and chemoattractant implicated in several biological processes, including cell survival, proliferation, and migration. In this study, we investigated the effect of cigarette smoke extract (CSE) on cell proliferation of rat pulmonary artery smooth muscle cells (rPASMCs). We found that stimulation of rPASMCs with CSE significantly increased cell proliferation and promoted cell cycle progression from G1 phase to the S and G2 phases. CSE treatment also significantly upregulated the mRNA and protein levels of PDGFB and PDGFRβ. Our study also revealed that Rottlerin, an inhibitor of PKCδsignaling, prevented CSE-induced cell proliferation, attenuated the increase of S and G2 phase populations induced by CSE treatment, and downregulated PDGFB and PDGFRβmRNA and protein levels in rPASMCs exposed to CSE. Collectively, our data demonstrated that CSE-induced cell proliferation of rPASMCs involved upregulation of the PKCδ-PDGFB pathway.

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 Prohibitin protects against cigarette smoke extract-induced cell apoptosis in cultured human pulmonary microvascular endothelial cells

2020 ◽  
Author(s):  
Yating Peng ◽  
Zijing Zhou ◽  
Aiyuan Zhou ◽  
JiaXi Duan ◽  
Hong Peng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cigarette Smoke ◽  
Cell Apoptosis ◽  
Cigarette Smoke Extract ◽  
Microvascular Endothelial Cells ◽  
Cigarette Smoke Exposure ◽  
Dependent Manner ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Mitochondrial Transcription Factor ◽  
Microvascular Endothelial

Prohibitin is an evolutionarily conserved and ubiquitously expressed protein in eukaryocyte. It mediate many important roles in cell survival, apoptosis, autophagy and senescence. In the present study, we aimed to explore the role of prohibitin in cigarette smoke extract (CSE)-induced apoptosis of human pulmonary microvascular endothelial cells (HPMECs). For this purpose, HPMECs were trasfected with prohibitin and challenged with CSE. Our results showed that CSE exposure inhibited prohibitin expression in a dose-dependent manner in HPMECs. Overexpression of prohibitin could protect cell from CSE-induced injury by inhibiting CSE-induced cell apoptosis, inhibiting reactive oxygen species (ROS) production, increase mitochondrial membrane potential, increase the content of mitochondrial transcription factor A (mtTFA), IKKα/β phosphorylation and IκB-α degradation. CSE decreases prohibitin expression in endothelial cells and restoration of prohibitin expression in these cells can protect against the deleterious effects of CSE on mitochondrial and cells. We identified prohibitin is a novel regulator of endothelial cell apoptosis and survival in the context of cigarette smoke exposure.

Sign in / Sign up

Export Citation Format

Share Document