Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium

Murray, Lynne A.; Dunmore, Rebecca; Camelo, Ana Paula; Silva, Carla A. Da; Gustavsson, Malin; Habiel, David M.; Hackett, Tillie L.; Hogaboam, Cory M.; Sleeman, Matthew A.; Knight, Darryl A.

doi:10.1186/s12931-017-0565-2

Cited by 27 publications

(18 citation statements)

References 34 publications

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“…6,7 Cell death induced by smoking may trigger a local or systemic inflammatory response that results in endothelial cell activation, the promotion of a prothrombotic stage and atherosclerotic plaque formation. 8,9 The extent of systemic inflammation can be assessed by the plasma Creactive protein (CRP) levels. 10 head and neck cancer patients, independently of tumournode-metastasis (TNM) staging.…”

Section: Introductionmentioning

confidence: 99%

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Luetragoon

Rutqvist²,

Tangvarasittichai

et al. 2018

Immunology

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Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8 cells in the lymphocyte group, CD13 CD11 , CD13 CD14 , CD13 CD56 cells in the monocyte group and CD13 CD11 , CD13 CD56 cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8 GZB cells in the CD8 group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.

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Section: Introductionmentioning

confidence: 99%

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Luetragoon

Rutqvist²,

Tangvarasittichai

et al. 2018

Immunology

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“…1 Bronchial epithelial cells (BECs) are involved in the pathophysiology of COPD through the release of cytokines and chemokines in response to cigarette smoke. 2 COPD exacerbations are an acute worsening of symptoms, often caused by viral or bacterial infection and resulting in further amplification of airway inflammation. 3 Inhaled corticosteroids (ICS) are anti-inflammatory drugs that prevent exacerbations and improve quality of life in COPD patients.…”

Section: Introductionmentioning

confidence: 99%

Differential anti-inflammatory effects of budesonide and a p38 MAPK inhibitor AZD7624 on COPD pulmonary cells

Higham¹,

Karur²,

Jackson³

et al. 2018

Airway Pharmacology and Treatment

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Background: The effects of anti-inflammatory drugs in COPD patients may vary between different cell types. The aim of the current study was to assess the anti-inflammatory effects of the corticosteroid budesonide and a p38 MAPK inhibitor (AZD7624) on different cell types obtained from COPD patients and healthy controls. Methods: Eight healthy smokers, 16 COPD infrequent exacerbators, and 16 frequent COPD exacerbators ($2 exacerbations in the last year) were recruited for bronchoscopy and blood sampling. The anti-inflammatory effects of budesonide and AZD7624 were assessed on cytokine release from lipopolysaccharide-stimulated alveolar macrophages and peripheral blood mononuclear cells and polyinosinic:polycytidylic acid-stimulated bronchial epithelial cells. Results: The anti-inflammatory effects of budesonide varied greatly within a patient according to the cell type studied. Bronchial epithelial cells showed the lowest sensitivity to budesonide, while peripheral blood mononuclear cells showed the greatest sensitivity. AZD7624 had a greater effect than budesonide on cytokine production from bronchial epithelial cells. Exacerbation frequency did not influence corticosteroid sensitivity. Conclusion: We observed variable corticosteroid and p38 MAPK inhibitor anti-inflammatory responses within the same individual depending on the cell type studied. These findings support the use of multiple anti-inflammatory strategies in COPD patients due to differences between cell types.

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“…EMT in COPD may be activated by interactions among epithelial cells and fibroblasts [227], reminiscent of non-cell autonomous regulation of EMT in lung cancer [228]. A recent report showed that the acute effects of cigarette smoke and associated infection, together play an important role in driving complete EMT; thus an extra insult, such as an infection can further exaggerate EMT [76] leading to chronically remodelled airways as observed in COPD [229].…”

Section: Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Eapen

Hansbro

Larsson‐Callerfelt

et al. 2018

Drugs

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COPD and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking, and exert a considerable societal burden. People suffering from COPD are at a higher risk of developing lung cancer than those without COPD and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower post-operative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we shall provide a detailed overview of possible underlying factors that link COPD and lung cancer and current therapeutic advances from both human and pre-clinical animal models that can effectively mitigate this unholy relationship. Running head-COPD and lung cancer: understanding and treatments

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Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium

Cited by 27 publications

References 34 publications

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals

Differential anti-inflammatory effects of budesonide and a p38 MAPK inhibitor AZD7624 on COPD pulmonary cells

Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

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