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

Molecules ◽  
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.

scholarly journals Cigarette smoke induction of S100A9 contributes to chronic obstructive pulmonary disease

2020 ◽  
Vol 319 (6) ◽  
pp. L1021-L1035
Author(s):  
Christopher Railwah ◽  
Alnardo Lora ◽  
Kanza Zahid ◽  
Hannah Goldenberg ◽  
Michael Campos ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Extracellular Matrix ◽  
Lung Function ◽  
Matrix Metalloproteinase ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Acute And Chronic Exposure

S100 calcium-binding protein A9 (S100A9) is elevated in plasma and bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9-mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9 were higher in older mice compared with in young animals and coincided with pulmonary function changes. Both acute and chronic exposure to cigarette smoke enhanced S100A9 levels in age-matched mice. To examine the direct role of S100A9 on the development of COPD, S100a9−/− mice or mice administered paquinimod were exposed to chronic cigarette smoke. S100A9 depletion and inhibition attenuated the loss of lung function, pressure-volume loops, airway inflammation, lung compliance, and forced expiratory volume in 0.05 s/forced vital capacity, compared with age-matched wild-type or vehicle-administered animals. Loss of S100a9 signaling reduced cigarette smoke-induced airspace enlargement, alveolar remodeling, lung destruction, ERK and c-RAF phosphorylation, matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and keratinocyte-derived chemokine (KC) release into the airways. Paquinimod administered to nonsmoked, aged animals reduced age-associated loss of lung function. Since fibroblasts play a major role in the production and maintenance of extracellular matrix in emphysema, primary lung fibroblasts were treated with the ERK inhibitor LY3214996 or the c-RAF inhibitor GW5074, resulting in less S100A9-induced MMP-3, MMP-9, MCP-1, IL-6, and IL-8. Silencing Toll-like receptor 4 (TLR4), receptor for advanced glycation endproducts (RAGE), or extracellular matrix metalloproteinase inducer (EMMPRIN) prevented S100A9-induced phosphorylation of ERK and c-RAF. Our data suggest that S100A9 signaling contributes to the progression of smoke-induced and age-related COPD.

scholarly journals Chemerin: A Potential Regulator of Inflammation and Metabolism for Chronic Obstructive Pulmonary Disease and Pulmonary Rehabilitation

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Jian Li ◽  
Yufan Lu ◽  
Ning Li ◽  
Peijun Li ◽  
Zhengrong Wang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lipid Metabolism ◽  
Pulmonary Disease ◽  
Inflammatory Responses ◽  
Therapeutic Interventions ◽  
Chronic Obstructive ◽  
Barrier Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Glucose And Lipid Metabolism

Chronic obstructive pulmonary disease (COPD) features chronic inflammatory reactions of both intra- and extrapulmonary nature. Moreover, COPD is associated with abnormal glucose and lipid metabolism in patients, which influences the prognosis and chronicity of this disease. Abnormal glucose and lipid metabolism are also closely related to inflammation processes. Further insights into the interactions of inflammation and glucose and lipid metabolism might therefore inspire novel therapeutic interventions to promote lung rehabilitation. Chemerin, as a recently discovered adipokine, has been shown to play a role in inflammatory response and glucose and lipid metabolism in many diseases (including COPD). Chemerin recruits inflammatory cells to sites of inflammation during the early stages of COPD, leading to endothelial barrier dysfunction, early vascular remodeling, and angiogenesis. Moreover, it supports the recruitment of antigen-presenting cells that guide immune cells as part of the body’s inflammatory responses. Chemerin also regulates metabolism via activation of its cognate receptors. Glucose homeostasis is affected via effects on insulin secretion and sensitivity, and lipid metabolism is changed by increased transformation of preadipocytes to mature adipocytes through chemerin-binding receptors. Controlling chemerin signaling may be a promising approach to improve various aspects of COPD-related dysfunction. Importantly, several studies indicate that chemerin expression in vivo is influenced by exercise. Although available evidence is still limited, therapeutic alterations of chemerin activity may be a promising target of therapeutic approaches aimed at the rehabilitation of COPD patients based on exercises. In conclusion, chemerin plays an essential role in COPD, especially in the inflammatory responses and metabolism, and has a potential to become a target for, and a biomarker of, curative mechanisms underlying exercise-mediated lung rehabilitation.

scholarly journals Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Dexun Hao ◽  
Yanshuang Li ◽  
Jiang Shi ◽  
Junguang Jiang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Cell Viability ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction and progressive lung inflammation. As the primary ingredient of a traditional Chinese medical herb, Baicalin has been previously shown to possess anti-inflammatory abilities. Thus, the current study aimed to elucidate the mechanism by which baicalin alleviates COPD. Methods Baicalin was adopted to treat cigarette smoke in extract-exposed MLE-12 cells after which cell viability and apoptosis were determined. The production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8 were determined by enzyme-linked immunoassay. A COPD mouse model was constructed via exposure to cigarette smoke and lipopolysaccharide, baicalin treatment. Lung function and inflammatory cell infiltration were determined and the production of Muc5AC, TNF-α, IL-6, IL-8 in the bronchoalveolar lavage fluid (BALF) was assayed by ELISA. The effect of HSP72 and JNK on COPD following treatment with baicalin was assessed both in vivo and in vitro by conducting loss- and gain- function experiments. Results Baicalin improved lung function evidenced by reduction in inflammatory cell infiltration and Muc5AC, TNF-α, IL-6 and IL-8 levels observed in BALF in mice. Baicalin was further observed to elevate cell viability while inhibited apoptosis and TNF-α, IL-6 and IL-8 levels in MLE-12 cells. Baicalin treatment increased HSP72 expression, while its depletion reversed the effect of baicalin on COPD. HSP72 inhibited the activation of JNK, while JNK activation was found to inhibit the effect of baicalin on COPD. Conclusions Baicalin upregulated the expression of HSP72, resulting in the inhibition of JNK signaling activation, which ultimately alleviates COPD.

scholarly journals HIF-1α Contributes to the Progression of Chronic Obstructive Pulmonary Disease

2022 ◽  
Author(s):  
Kedong Zhang ◽  
Feng Zhou ◽  
Caixia Zhu ◽  
Liang Yuan ◽  
Defu Li ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
A549 Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tgf Β1

Background: Hypoxia-inducible factor-1α (HIF-1α) plays an important regulatory role in inflammatory and hypoxic diseases. Higher HIF-1α level was found in lungs of chronic obstructive pulmonary disease (COPD) patients, however, its role in cigarette smoke (CS)-induced COPD has not been fully studied. Digoxin has been showed to inhibit HIF-1α translation and block HIF-1α activity and thus is often used as the HIF-1α inhibitor. Therefore, in the present study, we chose digoxin as the inhibitor to investigate whether HIF-1α contributes to the progression of COPD and possible mechanism. Methods: CS-exposed mice were intragastrically treated with different doses of digoxin, and COPD-associated phenotypes such as pathological changes in lungs, inflammation, lung function and mucus secretion in airways were evaluated. Meanwhile, CSE-treated A549 cells were administrated with digoxin or S7959. Moreover, EMT-associated markers together with HIF-1α\TGF-β1\Smad3 signaling pathway were detected both in vivo and in vitro. Results: The level of HIF-1α was significantly increased in lungs of COPD mice and CSE-exposed A549 cells, which was markedly suppressed by digoxin. Moreover, digoxin inhibited CS-induced inflammatory responses, lung function decline, and mucus hyper-secretion in COPD mouse model. In in vitro studies, digoxin decreased CSE-induced pro-inflammatory cytokine release. Importantly, CS-induced or CSE-induced EMT and up-regulation of HIF-1α/TGF-β1/Smad pathway was inhibited by digoxin. Additionally, S7959 mitigated CSE-induced EMT in A549 cells. Conclusions: Digoxin can protect CS-induced COPD and prevent CS-induced EMT possibly through HIF-1α/TGF-β1/Smad3 signaling pathway. This study suggests HIF1-α could be a potential intervention target for COPD prevention and treatment, especially for EMT in CS-induced COPD.

scholarly journals Clinical significance of changes in serum inflammatory factors in patients with chronic obstructive pulmonary disease and pulmonary infection

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110132
Author(s):  
Jun Zhou ◽  
Feng Jin ◽  
Feng Wu
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Pulmonary Infection ◽  
Inflammatory Responses ◽  
White Blood Cells ◽  
Inflammatory Factors ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α

Background Chronic obstructive pulmonary disease (COPD) is often accompanied by pulmonary infection, inflammatory responses, decreased immunity, and decreased lung function. The relationships among the pulmonary inflammation index (PII), lung function, and immunity in COPD patients with pulmonary infection remain unclear. Methods This retrospective observational study enrolled 234 participants (patients with COPD and pulmonary infection, patients with COPD without pulmonary infection, and healthy individuals) from January 2017 to December 2019. Results Levels of interleukin (IL)-6 were lower and levels of IL-8 were higher in patients with COPD and pulmonary infection. Levels of white blood cells (WBCs), C-reactive protein (CRP), IL-6, IL-8, tumor necrosis factor (TNF)-α and CD8+ cells were higher, while levels of CD3+ and CD4+ cells, the CD4+/CD8+ ratio, forced expiratory volume in 1 s (FEV1), FEV1 % predicted (FEV1%pred), and FEV1/forced vital capacity (FVC) (FEV1%FVC) were lower in patients with COPD and pulmonary infection. Levels of WBCs, CRP, IL-6, IL-8, and TNF-α were negatively associated with FEV1, FEV1%pred and FEV1%FVC. Conclusions Patients with COPD and pulmonary infection have high PIIs, decreased immunity, and poor lung function. PII is closely related to lung function and may represent a useful biomarker for the assessment of patients with COPD and pulmonary infection.

Screening of High-risk Patients for Chronic Obstructive Pulmonary Disease in Primary Care: A Narrative Review (Preprint)

2020 ◽  
Author(s):  
Ponrathi Athilingam ◽  
Andrew Bugajski ◽  
Usha Menon
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Current Knowledge ◽  
Screening Tools ◽  
Chronic Obstructive ◽  
Early Screening ◽  
Obstructive Pulmonary Disease ◽  
Impaired Lung Function ◽  
Risk Patients

UNSTRUCTURED Chronic obstructive pulmonary disease (COPD) predominantly affects older adults, and claimed 3 million lives in 2016, making it the third leading cause of death worldwide. Over 35 million Americans aged 40 or older have lung function consistent with diagnosable COPD. COPD and cardiovascular disease (CVD) have a bidirectional relationship, in that one is a risk factor for developing the other. National and international consortiums recommend early screening of adults at risk of COPD, such as those with CVD. Recommended screening strategies include screening tools to assess symptoms, medical history, and handheld spirometry. Handheld spirometry has high diagnostic accuracy and if impaired lung function is indicated, these patients are referred for pulmonary function testing (PFT), the diagnostic gold standard for COPD. However, there is no clinical consensus for pulmonary screening in people with CVD. Current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence is key in combating the global burden of COPD.

Sign in / Sign up

Export Citation Format

Share Document