Cigarette Smoke Increases Endothelial CXCL16-Leukocyte CXCR6 Adhesion In Vitro and In Vivo. Potential Consequences in Chronic Obstructive Pulmonary Disease

The increased morbidity, mortality, and ineffective treatment associated with the pathogenesis of chronic inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD) have generated much research interest. The key role is played by phospholipases from the A2superfamily: enzymes which are involved in inflammation through participation in pro- and anti-inflammatory mediators production and have an impact on many immunocompetent cells. The 30 members of the A2superfamily are divided into 7 groups. Their role in asthma and COPD has been studiedin vitroandin vivo(animal models, cell cultures, and patients). This paper contains complete and updated information about the involvement of particular enzymes in the etiology and course of asthma and COPD.

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miR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.551839 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weiwei Yu ◽

Ting Ye ◽

Jie Ding ◽

Yi Huang ◽

Yang Peng ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Tight Junction ◽

Pulmonary Disease ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Healthy Controls ◽

Rt Pcr ◽

Obstructive Pulmonary Disease

Background: Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown.Objectives: To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, both in vivo and in vitro.Methods: We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group.Results: The in vivo and in vitro results showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3′-UTR of CCL3.Conclusion: miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.

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Endothelial Progenitor Cells as Pathogenetic and Diagnostic Factors, and Potential Targets for GLP-1 in Combination with Metabolic Syndrome and Chronic Obstructive Pulmonary Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20051105 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1105 ◽

Cited By ~ 3

Author(s):

Evgenii Skurikhin ◽

Olga Pershina ◽

Angelina Pakhomova ◽

Edgar Pan ◽

Vyacheslav Krupin ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Metabolic Syndrome ◽

Endothelial Cells ◽

Progenitor Cells ◽

Pulmonary Disease ◽

Endothelial Progenitor Cells ◽

Cigarette Smoke ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

In clinical practice, there are patients with a combination of metabolic syndrome (MS) and chronic obstructive pulmonary disease (COPD). The pathological mechanisms linking MS and COPD are largely unknown. It remains unclear whether the effect of MS (possible obesity) has a major impact on the progression of COPD. This complicates the development of effective approaches for the treatment of patients with a diagnosis of MS and COPD. Experiments were performed on female C57BL/6 mice. Introduction of monosodium glutamate and extract of cigarette smoke was modeled to simulate the combined pathology of lipid disorders and emphysema. Biological effects of glucagon-like peptide 1 (GLP-1) and GLP-1 on endothelial progenitor cells (EPC) in vitro and in vivo were evaluated. Histological, immunohistochemical methods, biochemical methods, cytometric analysis of markers identifying EPC were used in the study. The CD31+ endothelial cells in vitro evaluation was produced by Flow Cytometry and Image Processing of each well with a Cytation™ 3. GLP-1 reduces the area of emphysema and increases the number of CD31+ endothelial cells in the lungs of mice in conditions of dyslipidemia and damage to alveolar tissue of cigarette smoke extract. The regenerative effects of GLP-1 are caused by a decrease in inflammation, a positive effect on lipid metabolism and glucose metabolism. EPC are proposed as pathogenetic and diagnostic markers of endothelial disorders in combination of MS with COPD. Based on GLP-1, it is proposed to create a drug to stimulate the regeneration of endothelium damaged in MS and COPD.

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The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease

Molecules ◽

10.3390/molecules26216588 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6588

Author(s):

Je-Oh Lim ◽

Woong-Il Kim ◽

Se-Jin Lee ◽

So-Won Pak ◽

Young-Kwon Cho ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Pulmonary Disease ◽

Cigarette Smoke ◽

Inflammatory Responses ◽

Chronic Obstructive ◽

Melatonin Treatment ◽

Obstructive Pulmonary Disease ◽

Camp Levels

Chronic obstructive pulmonary disease (COPD) is a significant disease threatening human health. Currently, roflumilast, a phosphodiesterase (PDE)4 inhibitor, is recommended as a therapeutic agent for COPD. In this study, we investigated the therapeutic effects of melatonin against COPD, focusing on determining whether it is a PDE4 inhibitor via in vivo and in vitro experiment using cigarette smoke (CS) and cigarette smoke condensate (CSC), respectively. In the in vivo experiments, melatonin treatment reduced inflammatory responses, including inflammatory cell counts. Melatonin treatment also suppressed the CS-exposure-induced upregulation of cytokine and matrix metalloproteinase (MMP)-9, reduced the PDE4B expression, and elevated cAMP levels. In addition, these effects were synergistic, as melatonin and roflumilast cotreatment eventually ameliorated the CS-exposure-induced worsening of lung function. In the CSC-stimulated NCI-H292 cells, melatonin inhibited elevation in the levels of inflammatory cytokines, MMP-9, and PDE4, and elevated cAMP levels. Furthermore, melatonin and roflumilast cotreatment was more effective on inflammatory responses than only melatonin or roflumilast treatment. Our results indicate that melatonin relieves inflammatory response and loss of lung function in COPD, which is associated with decreased PDE4 expression. Therefore, we suggest that melatonin is a putative candidate for the treatment of COPD.

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Ephedrine ameliorates chronic obstructive pulmonary disease (COPD) through restraining endoplasmic reticulum (ER) stress in vitro and in vivo

International Immunopharmacology ◽

10.1016/j.intimp.2021.107842 ◽

2022 ◽

Vol 103 ◽

pp. 107842

Author(s):

Hong-Lei Wang ◽

Fen-Qiao Chen ◽

Li-Juan Wu

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Pulmonary Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

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In vivo neutrophil sequestration within lungs of humans is determined by in vitro "filterability"

Journal of Applied Physiology ◽

10.1152/jappl.1991.71.5.1996 ◽

1991 ◽

Vol 71 (5) ◽

pp. 1996-2003 ◽

Cited By ~ 44

Author(s):

C. Selby ◽

E. Drost ◽

P. K. Wraith ◽

W. MacNee

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Normal Subjects ◽

Chronic Obstructive ◽

Cell Deformability ◽

Obstructive Pulmonary Disease ◽

Neutrophil Sequestration ◽

In Transit

Neutrophils are normally delayed in transit through the lung microcirculation, relative to the passage of erythrocytes. This sequestration contributes to a pulmonary pool of neutrophils that may relate to the relative inability of neutrophils to deform compared with erythrocytes when in transit in the pulmonary capillaries. A micropore membrane was used to model the human pulmonary microcirculation, in which cell deformability was measured as the pressure developed during filtration of the cells through the membrane at a constant flow. We demonstrated a significant correlation between in vitro deformability and in vivo lung sequestration of indium-111-labeled neutrophils in 10 normal subjects (r = 0.69, P less than 0.02). In eight patients with stable chronic obstructive pulmonary disease, this relationship was not significant (r = -0.2, P greater than 0.05). Furthermore, in a subject with microscopic pulmonary telangiectasia known to allow significant passage of 30-microns microspheres, neutrophils passed through the lungs without delay. Moreover, neutrophils from patients studied acutely with an exacerbation of chronic obstructive pulmonary disease were temporarily less deformable (P less than 0.01). These studies confirm that cell deformability is an important determinant of the normal neutrophil sequestration within the lungs. Changes in cell deformability may alter the extent of this sequestration.

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Tocotrienols: Dietary Supplements for Chronic Obstructive Pulmonary Disease

Antioxidants ◽

10.3390/antiox10060883 ◽

2021 ◽

Vol 10 (6) ◽

pp. 883

Author(s):

Xiangming Ji ◽

Hongwei Yao ◽

Maureen Meister ◽

Douglas S. Gardenhire ◽

Huanbiao Mo

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Chronic Bronchitis ◽

Pulmonary Disease ◽

Significant Risk ◽

Chronic Obstructive ◽

Alveolar Wall ◽

Obstructive Pulmonary Disease ◽

Anti Inflammatory

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Emphysema and chronic bronchitis are the two major phenotypes of COPD, which have many symptoms, such as dyspnea, chronic cough, and mucus overproduction. Emphysema is characterized by the destruction of the alveolar wall, while chronic bronchitis is characterized by limitations in expiratory airflow. Cigarette smoking is the most significant risk factor for the pathogenesis of COPD in the developed world. Chronic inflammation contributes to the onset and progression of the disease and furthers the risk of comorbidities. Current treatment options and prevention strategies for COPD are very limited. Tocotrienols are a group of vitamin E molecules with antioxidant and anti-inflammatory properties. Individual tocotrienols (α, γ, and δ) have shown their ability to attenuate inflammation specifically via suppressing nuclear factor-κB-mediated cytokine production. The δ- and γ-forms of tocotrienols have been indicated as the most effective in the prevention of macrophage infiltration, production of reactive oxygen species, and cytokine secretion. This review briefly discusses the pathogenesis of COPD and the role of inflammation therein. Furthermore, we summarize the in vitro and in vivo evidence for the anti-inflammatory activity of tocotrienols and their potential application to COPD management. Coupled with the bioavailability and safety profile of tocotrienols, the ability of these compounds to modulate COPD progression by targeting the inflammation pathways renders them potential candidates for novel therapeutic approaches in the treatment of COPD patients.

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