scholarly journals CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice

2021 ◽  
Vol 14 (7) ◽  
pp. 620
Author(s):  
Maximiliano Ruben Ferrero ◽  
Cristiana Couto Garcia ◽  
Marcella Dutra de Almeida ◽  
Jullian Torres Braz da Silva ◽  
Daniella Bianchi Reis Insuela ◽  
...  
Keyword(s):  
Survival Rate ◽  
Cigarette Smoke ◽  
Influenza A ◽  
Oral Treatment ◽  
Neutrophil Infiltration ◽  
Serum Levels ◽  
Ccr5 Antagonist ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Acute Exacerbations

Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways, we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflammatory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6 mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc (10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD.

scholarly journals The Expression of IL-6, TNF-α, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jingtong Zheng ◽  
Yue Shi ◽  
Lingxin Xiong ◽  
Weijie Zhang ◽  
Ying Li ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Viral Infection ◽  
Pulmonary Disease ◽  
Influenza A ◽  
Clinical Symptoms ◽  
Inflammatory Diseases ◽  
Induced Sputum ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Acute Exacerbations

Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p<0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p>0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.

scholarly journals Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products

2010 ◽  
Vol 298 (2) ◽  
pp. L261-L269 ◽  
Author(s):  
Mirella Profita ◽  
Angelo Sala ◽  
Anna Bonanno ◽  
Loredana Riccobono ◽  
Maria Ferraro ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Neutrophil Infiltration ◽  
Receptor Expression ◽  
Induced Sputum ◽  
Epithelial Cell Line ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cox 2

Cigarette smoke is the main cause of chronic obstructive pulmonary disease (COPD), where it can contribute to the observed airway inflammation. PGE2 is produced within human airways, and both pro- and anti-inflammatory activities have been reported. We quantitated PGE2 concentrations in induced sputum supernatants from different groups of subjects and correlated the obtained values to neutrophil infiltration as well as to the expression of cyclooxygenase-2 (COX-2). Cigarette smoke extract (CSE) was used to evaluate the effect of smoking on COX-2 and PGE2 receptor expression as well as on PGE2 release in neutrophils and alveolar macrophages (AM) obtained from normal donors. The effects of PGE2 and of PGE receptor agonists and antagonists were evaluated on the adhesion of neutrophil to a human bronchial epithelial cell line (16HBE). PGE2 levels, COX-2 expression, and neutrophil infiltration were significantly higher in normal smokers and COPD smokers ( P < 0.0001) compared with controls and COPD former smokers. Induced sputum supernatant caused neutrophil adhesion to 16HBE that was significantly reduced, in COPD smokers only, by PGE2 immunoprecipitation. In vitro experiments confirmed that CSE increased PGE2 release and COX-2 and PGE2 receptor expression in neutrophils and AM; PGE2 enhanced the adhesion of neutrophils to 16HBE, and a specific E-prostanoid 4 (EP4) receptor antagonist blunted its effect. These results suggest that CSE promote the induction of COX-2 and contributes to the proinflammatory effects of PGE2 in the airways of COPD subjects.

Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory changes in rat lung and the role of CXCR2 ligands in mediating this effect

2005 ◽  
Vol 288 (3) ◽  
pp. L514-L522 ◽  
Author(s):  
Christopher S. Stevenson ◽  
Kevin Coote ◽  
Ruth Webster ◽  
Helinor Johnston ◽  
Hazel C. Atherton ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Neutrophil Migration ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Whole Body ◽  
Chronic Obstructive ◽  
Dependent Manner ◽  
Obstructive Pulmonary Disease ◽  
Rat Growth ◽  
Inflammatory Changes

Repetitive, acute inflammatory insults elicited by cigarette smoke (CS) contribute to the development of chronic obstructive pulmonary disease (COPD), a disorder associated with lung inflammation and mucus hypersecretion. Presently, there is a poor understanding of the acute inflammatory mechanisms involved in this process. The aims of this study were to develop an acute model to investigate temporal inflammatory changes occurring after CS exposure. Rats were exposed to whole body CS (once daily) generated from filtered research cigarettes. Initial studies indicated the generation of a neutrophilic/mucus hypersecreting lung phenotype in <4 days. Subsequent studies demonstrated that just two exposures to CS (15 h apart) elicited a robust inflammatory/mucus hypersecretory phenotype that was used to investigate mechanisms driving this response. Cytokine-induced neutrophil chemoattractants (CINCs) 1–3, the rat growth-related oncogene-α family homologs, and IL-1β demonstrated time-dependent increases in lung tissue or lavage fluid over the 24-h period following CS exposure. The temporal changes in the neutrophil chemokines, CINCs 1–3, mirrored increases in neutrophil infiltration, indicative of a role in neutrophil migration. In addition, a specific CXCR2 antagonist, SB-332235, effectively inhibited CS-induced neutrophilia in a dose-dependent manner, supporting this conclusion. This modeling of the response of the rat airways to acute CS exposure indicates 1) as few as two exposures to CS will induce a phenotype with similarities to COPD and 2) a novel role for CINCs in the generation of this response. These observations represent a paradigm for the study of acute, repetitive lung insults that contribute to the development of chronic disease.

scholarly journals α,β-Unsaturated aldehydes contained in cigarette smoke elicit IL-8 release in pulmonary cells through mitogen-activated protein kinases

2009 ◽  
Vol 296 (5) ◽  
pp. L839-L848 ◽  
Author(s):  
Nadia Moretto ◽  
Fabrizio Facchinetti ◽  
Thomas Southworth ◽  
Maurizio Civelli ◽  
Dave Singh ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Neutrophil Infiltration ◽  
Acute Effect ◽  
Airway Epithelial Cells ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Obstructive Pulmonary Disease ◽  
Unsaturated Aldehydes ◽  
Cytokines And Chemokines

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD), a syndrome characterized by pulmonary neutrophil infiltration, chronic inflammation, and progressive tissue destruction. We examined here the acute effect of aqueous cigarette smoke extract (CSE) and of two α,β-unsaturated aldehydes (acrolein and crotonaldehyde) contained in CSE in cultured normal human lung fibroblasts and small airway epithelial cells. By examining a panel of 19 cytokines and chemokines, we found that IL-8 release was elevated by CSE as well as by acrolein, whereas other inflammatory mediators were mostly unaffected. CSE-evoked IL-8 release was mimicked by acrolein and crotonaldehyde at concentrations (3–60 μM each) found in CSE and fully prevented by 1 mM α,β-unsaturated aldehydes scavengers N-acetylcysteine (NAC) or sodium 2-mercaptoethanesulfonate. Neither the saturated aldehyde acetaldehyde nor H2O2 evoked IL-8 release. In addition, CSE or crotonaldehyde upregulated the release of IL-8 from alveolar macrophages from both COPD patients and healthy nonsmokers, indicating that this is a response common to cells involved in lung inflammation. CSE-evoked IL-8 release was accompanied by increased phosphorylation of p38 MAPK and ERK1/2. CSE-evoked p38 and ERK1/2 phosphorylation was mimicked by acrolein and inhibited by NAC. IL-8 release elicited by both acrolein and CSE was blocked by pharmacological inhibition of p38 and ERK1/2 phosphorylation. In summary, our data show that α,β-unsaturated aldehydes-evoked phosphorylation of p38 and ERK1/2 underlies IL-8 release elicited by CSE, thus shedding light on the mechanisms through which cigarette smoke can initiate inflammation in the lung.

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