scholarly journals Isoforskolin Alleviates AECOPD by Improving Pulmonary Function and Attenuating Inflammation Which Involves Downregulation of Th17/IL-17A and NF-κB/NLRP3

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuang Xiao ◽  
Sha Cheng ◽  
Runfeng Li ◽  
Yutao Wang ◽  
Deyou Zeng ◽  
...  
Keyword(s):  
Viral Load ◽  
Pulmonary Function ◽  
Cigarette Smoke ◽  
Nlrp3 Inflammasome ◽  
Th17 Cells ◽  
Viral Infections ◽  
Nuclear Factor Κb ◽  
Lung Homogenate ◽  
The Body ◽  
Chronic Obstructive

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, is widely considered to be related to cigarette smoke (CS), and viral infections trigger acute exacerbation of COPD (AECOPD). Isoforskolin (ISOF) is a bioactive component from the plant Coleus forskohlii, native to Yunnan in China. It has been demonstrated that ISOF has anti-inflammatory effect on acute lung injury animal models. In the present study, we investigated the efficacy and mechanism of ISOF for the prevention and treatment of AECOPD. Mice were exposed to CS for 18 weeks and then infected with influenza virus A/Puerto Rico/8/34 (H1N1). ISOF (0.5, 2 mg/kg) was intragastrically administered once a day after 8 weeks of exposure to cigarette smoke when the body weight and lung function of model mice declined significantly. The viral load, pulmonary function, lung morphology, Th17 cells, and inflammatory cytokines in lung tissues were evaluated. The expression of nuclear factor κB (NF-κB) and NOD-like receptor pyrin domain–containing protein 3 (NLRP3) inflammasome pathways were detected. The results showed that ISOF treatment reduced the viral load in the lung homogenate, decreased the lung index of model mice, and lung pathological injuries were alleviated. ISOF also improved the pulmonary function with increased FEV0.1/FVC and decreased Rn and Rrs. The levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17A, MCP-1, MIG, IP-10, and CRP) in the lung homogenate were reduced after ISOF treatment. ISOF decreased the proportion of Th17 cells in the lung tissues by the flow cytometry test, and the protein expression levels of RORγt and p-STAT3 were also decreased. Furthermore, ISOF significantly inhibited the activation of NF-κB signaling and NLRP3 inflammasome in the lung tissues of model mice. In conclusion, ISOF alleviates AECOPD by improving pulmonary function and attenuating inflammation via the downregulation of proinflammatory cytokines, Th17/IL-17 A, and NF-κB/NLRP3 pathways.

scholarly journals Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4+ T Cells into Th17 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jifeng Liu ◽  
Xiaoning Zhong ◽  
Zhiyi He ◽  
Jianquan Zhang ◽  
Jing Bai ◽  
...  
Keyword(s):  
T Cells ◽  
Cigarette Smoke ◽  
Th17 Cells ◽  
Mixed Lymphocyte Reaction ◽  
Mononuclear Cells ◽  
Cigarette Smoke Extract ◽  
Exposed Group ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Cigarette smoke is a major effector of chronic obstructive pulmonary disease (COPD), and Th17 cells and dendritic cells (DCs) involve in the pathogenesis of COPD. Previous studies have demonstrated the anti-inflammatory effects of macrolides. However, the effects of macrolides on the cigarette smoke extract- (CSE-) induced immune response are unclear. Accordingly, in this study, we evaluated the effects of erythromycin (EM) on CSE-exposed DCs polarizing naïve CD4+ T cells into Th17 cells. DCs were generated from bone marrow-derived mononuclear cells isolated from male BALB/c mice and divided into five groups: control DC group, CSE-exposed DC group, CD40-antibody-blocked CSE-exposed DC group, and EM-treated CSE-exposed DC group. The function of polarizing CD4+ T cells into Th17 cells induced by all four groups of DCs was assayed based on the mixed lymphocyte reaction (MLR) of naïve CD4+ T cells. CD40 expression in DCs in the CSE-exposed group increased significantly compared with that in the control group (P<0.05). The Th17 cells in the CSE-exposed DC/MLR group increased significantly compared with those in the control DC/MLR group (P<0.05). Moreover, Th17 cells in the CD40-blocked CSE-exposed DC/MLR group and EM-treated CSE-exposed DC/MLR group were reduced compared with those in the CSE-exposed DC/MLR group (P<0.05). Thus, these findings suggested that EM suppressed the CSE-exposed DC-mediated polarization of CD4+ T cells into Th17 cells and that this effect may be mediated through inhibition of the CD40/CD40L pathway.

scholarly journals Cigarette Smoke Exposure Induces Retrograde Trafficking of CFTR to the Endoplasmic Reticulum

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Abigail J. Marklew ◽  
Waseema Patel ◽  
Patrick J. Moore ◽  
Chong D. Tan ◽  
Amanda J. Smith ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cigarette Smoke ◽  
Anion Channel ◽  
Airway Disease ◽  
Underlying Mechanism ◽  
The Body ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Retrograde Trafficking ◽  
Anion Secretion

Abstract Chronic obstructive pulmonary disease (COPD), which is most commonly caused by cigarette smoke (CS) exposure, is the third leading cause of death worldwide. The cystic fibrosis transmembrane conductance regulator (CFTR) is an apical membrane anion channel that is widely expressed in epithelia throughout the body. In the airways, CFTR plays an important role in fluid homeostasis and helps flush mucus and inhaled pathogens/toxicants out of the lung. Inhibition of CFTR leads to mucus stasis and severe airway disease. CS exposure also inhibits CFTR, leading to the decreased anion secretion/hydration seen in COPD patients. However, the underlying mechanism is poorly understood. Here, we report that CS causes CFTR to be internalized in a clathrin/dynamin-dependent fashion. This internalization is followed by retrograde trafficking of CFTR to the endoplasmic reticulum. Although this internalization pathway has been described for bacterial toxins and cargo machinery, it has never been reported for mammalian ion channels. Furthermore, the rapid internalization of CFTR is dependent on CFTR dephosphorylation by calcineurin, a protein phosphatase that is upregulated by CS. These results provide new insights into the mechanism of CFTR internalization, and may help in the development of new therapies for CFTR correction and lung rehydration in patients with debilitating airway diseases such as COPD.

scholarly journals Smoking tends to decrease glutathione and increase malondialdehyde levels in medical students

2016 ◽  
Vol 35 (2) ◽  
pp. 89 ◽  
Author(s):  
Safyudin Safyudin ◽  
Subandrate Subandrate
Keyword(s):  
Medical Students ◽  
Cigarette Smoke ◽  
The Body ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Toxic Substances ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Significant Difference ◽  
Endogenous Antioxidant

Background<br />Smoking is the act of introducing toxic substances into the body. Cigarette smoke contains chemicals that may cause several disorders, including cardiovascular disease, cancer, and chronic obstructive pulmonary disease. Toxic substances in cigarette smoke have the potential to increase free radicals, malondialdehyde (MDA) levels and to decrease endogenous antioxidant (glutathione/GSH) levels. This study aims to determine the relationship of smoking with plasma GSH and MDA levels in medical students.<br /><br />Methods<br />This study was analytical observational with cross-sectional approach. The study was conducted from April to December 2015. The subjects in this study were medical students, consisting of 20 smokers and 20 nonsmokers. Plasma GSH and MDA levels were determined biochemically using Sigma GSH Assay Kit and Sigma MDA Assay Kit. Data was analyzed using the independent t test. <br /><br />Results<br />The results showed that there was no significant difference between mean GSH in smokers (1.74 ± 0.91 mmol/L) and nonsmokers (2.42 ± 1.19 µmol/L) (p=0.441). Mean smokers MDA level of 2.06 ± 1.39 nmol/mL was not significantly different compared with mean nonsmokers MDA level (1.32 ± 0.90 nmol/mL) (p=0.092).<br /><br />Conclusions<br />Smoking tends to decrease plasma GSH levels and increase plasma MDA levels in medical students. Smoking history could be evidence of oxidative stress and an impaired oxidant defense system. In particular, young smokers should quit promptly before health problems arise, so as to have the optimal benefits of cessation.

scholarly journals Persistence of Th17/Tc17 Cell Expression upon Smoking Cessation in Mice with Cigarette Smoke-Induced Emphysema

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Min-Chao Duan ◽  
Hai-Juan Tang ◽  
Xiao-Ning Zhong ◽  
Ying Huang
Keyword(s):  
Smoking Cessation ◽  
Cigarette Smoke ◽  
Th17 Cells ◽  
Morphological Changes ◽  
Critical Role ◽  
T Cell Subsets ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Tc17 Cells

Th17 and Tc17 cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease caused predominantly by cigarette smoking. Smoking cessation is the only intervention in the management of COPD. However, even after cessation, the airway inflammation may be present. In the current study, mice were exposed to room air or cigarette smoke for 24 weeks or 24 weeks followed by 12 weeks of cessation. Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The frequencies of CD8+IL-17+(Tc17) and CD4+IL-17+(Th17) cells, the mRNA levels of ROR gamma and IL-17, and the levels of IL-8, TNF-alpha, and IFN-gamma in lungs or bronchoalveolar lavage fluid of mice were assayed. Here we demonstrated that alveolar enlargement and destruction induced by cigarette smoke exposure were irreversible and that cigarette smokeenhanced these T-cell subsets, and related cytokines were not significantly reduced after smoking cessation. In addition, the frequencies of Th17 and Tc17 cells in lungs of smoke-exposed mice and cessation mice were positively correlated with emphysematous lesions. More important, the frequencies of Tc17 cells were much higher than Th17 cells, and there was a significantly positive correlation between Th17 and Tc17. These results suggested that Th17/Tc17 infiltration in lungs may play a critical role in sustaining lung inflammation in emphysema. Blocking the abnormally increased numbers of Tc17 and Th17 cells may be a reasonable therapeutic strategy for emphysema.

scholarly journals Pengaruh Radikal Bebas Terhadap Proses Inflamasi pada Penyakit Paru Obstruktif Kronis (PPOK)

2018 ◽  
Vol 2 (4) ◽  
pp. 317
Author(s):  
Rivan Virlando Suryadinata
Keyword(s):  
Free Radicals ◽  
Cigarette Smoke ◽  
Reactive Oxygen ◽  
The Body ◽  
Reactive Nitrogen ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Metabolic Products ◽  
Inflammatory Processes ◽  
And Function

Background: Chronic Obstructive Pulmonary Disease is diseases caused by exposure to cigarette smoke. Cigarette smoke carries free radicals into the airways which can lead to acute exacerbations in patients.Objectives: explanation of inflammatory processes in the airways in patients with PPOK due to an increase in free radicals.Discusion: In the human body, free radicals are metabolic products from normal cells and function as one of the body's defense systems. Free radicals can be Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), both of which can be obtained from the inside (endogenous) or from outside the body (exogenous). In the pathological, exposure to cigarette smoke causes an imbalance between the amount of free radicals produced in the body so that it can lead to oxidative stress.Conclusion: An increase in the number of free radicals will directly affect inflammatory mediators in the body. Increased free radicals will trigger the inflammatory process locally in the airways and systemically, so increasing the rate of exacerbations in COPD patients.ABSTRAKLatar Belakang : Penyakit PPOK ditimbulkan akibat paparan asap rokok yang terus menerus. Radikal bebas yang dibawa oleh asap rokok terhirup masuk kedalam saluran napas dapat menimbulkan eksaserbasi.Tujuan : Menjelaskan proses eksaserbasi yang dipengaruhi oleh proses inflamasi pada penderita PPOK akibat peningkatan radikal bebas.Ulasan : Pada tubuh manusia, radikal bebas merupakan produk hasil metabolisme dari sel normal. Pada keadaan normal, Radikal bebas berfungsi sebagai salah satu sistem pertahanan tubuh. Radikal bebas dapat berupa Reactive Oxygen Spesies (ROS) dan Reactive Nitrogen Spesies (RNS), keduanya dapat diperoleh melalui dari dalam  (endogen) maupun dari luar tubuh (eksogen). Pada keadaan patologis akibat paparan asap rokok menimbulkan ketidakseimbangan antara jumlah radikal bebas yang dihasilkan dalam tubuh sehingga dapat mengakibatkan terjadinya stress oksidatif.Kesimpulan:Peningkatan jumlah radikal bebas secara langsung akan berpengaruh pada mediator inflamasi pada tubuh. Peningkatan radikal bebas akan memicu proses inflamasi secara lokal pada saluran napas dan sistemik sehingga meningkatkan angka kejadian eksaserbasi pada penderita PPOK. 

Il-17A contributes to maintenance of pulmonary homeostasis in a murine model of cigarette smoke-induced emphysema

2015 ◽  
Vol 309 (2) ◽  
pp. L188-L195 ◽  
Author(s):  
Meike Voss ◽  
Lisa Wolf ◽  
Andreas Kamyschnikow ◽  
Bodo Wonnenberg ◽  
Anja Honecker ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Cigarette Smoke ◽  
Murine Model ◽  
Lung Damage ◽  
Disease Assessment ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Lung Structure ◽  
Induced Changes

Smoking is the main risk factor for the development of the chronic obstructive pulmonary disease (COPD) in Western countries. Recent studies suggest that IL-17A and Th17 cells play a role in the pathogenesis of COPD. We used a murine model of chronic cigarette smoke (CS) exposure to explore the contribution of IL-17A to CS-induced lung damage and loss of pulmonary function. Histology and morphometry showed that IL-17A deficiency spontaneously resulted in a loss of lung structure under basal conditions. Even though inflammatory markers [IL-1β and granulocyte colony-stimulating factor (G-CSF)] were decreased in IL-17A-deficient mice (IL-17A−/−) exposed to CS compared with wild-type (WT) mice, IL-17A−/− mice were per se not protected from CS-induced emphysematous disease. Assessment of pulmonary function showed that IL-17A−/− mice were partially protected from CS-induced changes in total lung capacity. However, the respiratory elastance decreased and respiratory compliance increased in IL-17A−/− mice after exposure to CS. Morphometry revealed destruction of lung tissue in CS-exposed IL-17A−/− mice similar to WT mice. The expression of elastin was decreased in air-exposed IL-17A−/− mice and in CS-exposed WT and IL-17A−/− mice. Thus, in the present model of sterile CS-exposure, IL-17A contributes to normal lung homeostasis and does not mediate CS-induced loss of lung structure and pulmonary function.

scholarly journals The effects of the miR-21/SMAD7/TGF-β pathway on Th17 cell differentiation in COPD

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shengyang He ◽  
Shenghua Sun ◽  
Junjuan Lu ◽  
Lili Chen ◽  
Xiang Mei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cigarette Smoke ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Complex Disease ◽  
Signaling Molecules ◽  
Chronic Obstructive ◽  
T Helper 17 ◽  
Smad Signaling ◽  
Th17 Cell Differentiation

AbstractChronic obstructive pulmonary disease (COPD) is a complex disease with multiple etiologies, while smoking is the most established one. The present study investigated the modulation of T-helper 17 (Th17) cell differentiation by the miR-21/Smad7/TGF-β pathway, and their roles in COPD. Lung tissues were obtained from lung cancer patients with or without COPD who underwent lobotomy and the levels of miR-21, TGF-β/Smad signaling molecules, RORγT, and other Th17-related cytokines were detected. Mouse COPD models were built by exposing both wild-type (WT) and miR-21−/− mice to cigarette smoke (CS) and cigarette smoke extract (CSE) intraperitoneal injection. Isolated primary CD4+ T cells were treated with either CS extract, miR-21 mimics or inhibitors, followed by measuring Th17 cells markers and the expression of TGF-β/Smad signaling molecules and RORγT. Increased levels of miR-21, Smad7, phosphorylated (p)-Smad2, p-Smad3, TGF-β, and Th17-related cytokines was detected in the lungs of COPD patients. Lung function in modeled WT mice, but not miR-21−/− ones, deteriorated and the number of inflammatory cells in the lung tissues increased compared to the control WT-mice. Moreover, primary CD4+ lymphocytes tend to differentiate into Th17 cells after the treatment with CSE or miR-21 mimics, and the expression of RORγT and the TGF-β/Smad signaling were all increased, however miR-21 inhibitors worked reversely. Our findings demonstrated that Th17 cells increased under COPD pathogenesis and was partially modulated by the miR-21/Smad7/TGF-β pathway.

scholarly journals The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice

2021 ◽  
Author(s):  
Xuhua Yu ◽  
Tiantian Cai ◽  
Long Fan ◽  
Ziyao Liang ◽  
Qiuling Du ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Pulmonary Inflammation ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Smoke Exposure ◽  
Chronic Obstructive ◽  
Number Of Cells

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking has been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit anti-viral effects. Therefore, the aim of this study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of pro-inflammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1β. The results demonstrated that JPYFII formulation exerted an anti-viral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.

NLRP3 inflammasome expression in cultured hepatocytes is regulated by nuclear factor-κB (NF-κB)

2015 ◽  
Vol 53 (01) ◽  
Author(s):  
SG Boaru ◽  
E Borkham-Kamphorst ◽  
E Van de Leur ◽  
C Liedtke ◽  
R Weiskirchen
Keyword(s):  
Nlrp3 Inflammasome ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cultured Hepatocytes
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