scholarly journals Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 743-756 ◽  
Author(s):  
Chengyang Wang ◽  
Huanzhang Ding ◽  
Xiao Tang ◽  
Zegeng Li ◽  
Lei Gan
Keyword(s):  
Lung Function ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Interferon Γ ◽  
Normal Group ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Model Control ◽  
Stat Pathway

Background/Aims: To evaluate the effect of Liuweibuqi capsules on chronic obstructive pulmonary disease (COPD) through the JAK/STAT pathway. Methods: Lung function was measured with a spirometer. Changes in lung histology were observed using H&E staining. Cigarette smoke extract combined with lipopolysaccharide (CSE+LPS) was used to establish the cellular COPD model. Cytokine levels were determined using ELISA, and changes in the JAK/STAT pathway were evaluated using western blotting. The CCK8 method and flow cytometry were used to measure cell viability and apoptosis, respectively. Results: Liuweibuqi capsules reduced the damage in the lung tissues and the loss of lung function in the COPD rats. Additionally, the levels of interleukin (IL)-1β, interferon γ (IFNγ), IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were higher, whereas IL-10 was lower in the model control (MC) and CSE+LPS groups than in the normal group. The phosphorylation levels of JAK1, JAK2, STAT1, STAT3 and STAT5 were higher and the levels of SOCS1 and SOCS3 were lower in the MC group and CSE+LPS group compared with the normal group. After Liuweibuqi capsule treatment, the expression of inflammatory cytokines and elements of the JAK/STAT pathway were lower. In addition, over-expression of STAT3 blocked the effects of the Liuweibuqi capsules on the release of inflammatory cytokines, cell viability and apoptosis. Conclusion: Our findings suggested that Liuweibuqi capsule might effectively ameliorate the progression of COPD via the JAK/STAT pathway.

scholarly journals Effect of Liuweibuqi capsules on the balance between MMP-9 and TIMP1 and viability of alveolar macrophages in COPD

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Chengyang Wang ◽  
Huanzhang Ding ◽  
Xiao Tang ◽  
Zegeng Li ◽  
Lei Gan
Keyword(s):  
Lung Function ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Alveolar Macrophages ◽  
Serum Levels ◽  
Chronic Obstructive ◽  
High Dose ◽  
Group Model ◽  
Tnf Α ◽  
Model Control

The present study aims to investigate the effect of Liuweibuqi (LWBQ) capsules on the expression of matrix metalloproteinase (MMP)-9 and TIMP1 and cell viability of alveolar macrophages (AMs) in chronic obstructive pulmonary disease (COPD). Rats were randomly divided into normal control (NC) group, model control (MC) group, Jinshuibao (JSB) group, spleen aminopeptidase (PAT) group, and low dose of LWBQ (LWBQ low), mid dose of LWBQ (LWBQ mid), and high dose of LWBQ (LWBQ high) group (n=10). Lung function was measured with a spirometer. Serum cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected using ELISA. The expressions of MMP-9 and TIMP1 were detected by quantitative real-time PCR (qRT-PCR) and Western blot. MTT assay and flow cytometry were used to measure cell viability and apoptosis. Compared with the NC group, body weight and lung function were reduced in the MC group. In addition, the serum levels of IL-6 and TNF-α were higher in the MC group than those in the NC group. The expression of MMP-9 protein in the AMs from rats was higher, and TIMP1 protein was lower in the MC group compared with the NC group. After LWBQ capsules treatment, compared with the MC group, the expression of inflammatory cytokines and MMP-9 were lower and TIMP1 was higher. Moreover, after LWBQ-medicated serum treatment, the release of inflammatory cytokines was reduced from AMs. Besides, LWBQ-medicated serum decreased the expression of MMP-9 and increased the expression of TIMP1 and cell viability compared with those in MC group. In conclusion, LWBQ capsules can inhibit the release of inflammatory cytokines, promote cell viability in AMs, and regulate the expression of MMP-9 and TIMP1.

scholarly journals Exposure to Air Pollution Exacerbates Inflammation in Rats with Preexisting COPD

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Wang ◽  
Ya Li ◽  
Peng Zhao ◽  
Yange Tian ◽  
Xuefang Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Function ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Smoke Inhalation ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Collagen Iii ◽  
Pm2.5 Exposure

Particulate matter with an aerodynamic diameter equal or less than 2.5 micrometers (PM2.5) is associated with the development of chronic obstructive pulmonary disease (COPD). The mechanisms by which PM2.5 accelerates disease progression in COPD are poorly understood. In this study, we aimed to investigate the effect of PM2.5 on lung injury in rats with hallmark features of COPD. Cardinal features of human COPD were induced in a rat model by repeated cigarette smoke inhalation and bacterial infection for 8 weeks. Then, from week 9 to week 16, some of these rats with COPD were subjected to real-time concentrated atmospheric PM2.5. Lung function, pathology, inflammatory cytokines, oxidative stress, and mucus and collagen production were measured. As expected, the COPD rats had developed emphysema, inflammation, and deterioration in lung function. PM2.5 exposure resulted in greater lung function decline and histopathological changes, as reflected by increased Mucin (MUC) 5ac, MUC5b, Collagen I, Collagen III, and the profibrotic cytokine α-smooth muscle-actin (SMA), transforming growth factor- (TGF-) β1 in lung tissues. PM2.5 also aggravated inflammation, increasing neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF) and cytokines including Interleukin- (IL-) 1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-4. The likely mechanism is through oxidative stress as antioxidants levels were decreased, whereas oxidants were increased, indicating a detrimental shift in the oxidant-antioxidant balance. Altogether, these results suggest that PM2.5 exposure could promote the development of COPD by impairing lung function and exacerbating pulmonary injury, and the potential mechanisms are related to inflammatory response and oxidative stress.

The Effect of TGF-β1 Polymorphisms on Pulmonary Disease Progression in Patients with Cystic Fibrosis

2021 ◽  
Author(s):  
Tobias Trojan ◽  
Maxine von Maessenhausen ◽  
Peter Schneider ◽  
Gregor Fink ◽  
Ernst Rietschel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Disease Progression ◽  
Pulmonary Disease ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Genetic Modifier ◽  
Lung Function Decline ◽  
Tnf Α

Abstract Background: Transforming Growth Factor-β1 (TGF-β1) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-β1 are associated with neutrophilic inflammation, lung fibrosis und loss of pulmonary function.Aim: The aim of this study was to assess the relationship between genetic TGF-β1 polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-β1 polymorphisms on inflammatory cytokines in sputum were investigated.Methods: 56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-β1 sequence using the SNaPshot® technique. Individual slopes in forced expiratory volume in 1 second (FEV1) for all patients were calculated by using documented lung function values of the previous five years. The status of Pseudomonas aeruginosa (Pa) infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1β, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing.Results: The homozygous TT genotype at codon 10 was associated with a lower rate of chronic Pa infection (p<0.05). The heterozygous GC genotype at codon 25 was associated with lower lung function decline (p<0.05). Patients with homozygous TT genotype at the promotor SNP showed higher levels of TNF-α (p<0,05). Higher levels of TGF-β1 in plasma were associated with a more rapid FEV1 decline over five years (p<0.05). Conclusions: Our results suggest that polymorphisms in the TGF-β1 gene have an effect on lung function decline, Pa infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-β1 inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.

Electroacupuncture Reduces Hypothalamic and Medullary Expression of Orexins and their Receptors in a Rat Model of Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 36 (5) ◽  
pp. 312-318 ◽  
Author(s):  
Xin-Fang Zhang ◽  
Qin Qin ◽  
Wen-Ye Geng ◽  
Chuan-Wei Jiang ◽  
Yong Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Protein Expression ◽  
Pulmonary Function ◽  
Pulmonary Disease ◽  
Rat Model ◽  
Normal Group ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Objectives Decreased lung function in chronic obstructive pulmonary disease (COPD) is correlated with abnormal excitability of the respiratory centre where orexin neuropeptides from the hypothalamus are responsible for regulating respiration. We hypothesised that improvements in pulmonary function with electroacupuncture (EA) may be related to orexins in a rat model of COPD. Methods The COPD model was established by cigarette smoke exposure and lipopolysaccharide injection. Modelled rats received EA at BL13 and ST36 for two weeks, after which lung function was tested. Orexin levels in the hypothalamus and medulla were detected by ELISA, while mRNA/protein expression and localisation of orexins and their receptors were investigated using real time PCR, Western blotting and immunohistochemistry, respectively. Results The decrease in lung function observed in COPD rats was improved after EA treatment. Orexin levels in the hypothalamus and medulla were significantly higher in COPD rats than in normal rats, but were significantly reduced in the EA-treated group. There was a negative correlation between orexin content and lung function. In the hypothalamus, mRNA and protein expression and immunoreactivity of orexins were significantly higher in the COPD group than in the normal group, but a significant decrease was observed after EA. In the medulla, the expression and immunoreactivity of orexin receptors were significantly higher in the COPD group than in the normal group, but a significant decrease was observed after EA. Conclusions The positive effect of EA on pulmonary function in COPD rats may be related to downregulation of orexins and their receptors in the medulla.

scholarly journals Effects of plant-derived immunomodulators and lizak preparation in vitro taken separately or in combination on the immune factors of palatine tonsils of children with chronic tonsillitis

2020 ◽  
pp. 13-18
Author(s):  
Alexander Yu. Bredun ◽  
Oleg F. Melnikov ◽  
Мarina D. Timchenko
Keyword(s):  
Growth Factor ◽  
Cell Viability ◽  
Tissue Regeneration ◽  
Transforming Growth Factor ◽  
Interferon Γ ◽  
Interleukin 1Β ◽  
Combined Use ◽  
Antibacterial Preparation ◽  
Regeneration Factor

Introduction: Chronic inflammatory diseases of the upper respiratory tract of both microbial and viral origin occur due to the immune deficiency of systemic and local nature. Among a large number of immunomodulation agents, a special role belongs to plant preparations, which are characterized by relative harmlessness and high efficiency, both in case of systemic and local use and they are often combined with antimicrobial agents, therefore the aim of the study was to investigate their effect on the reactions and condition of lymphoid cells of tonsilswith separate and combined use in vitro. Methods: Cell suspensions were prepared mechanically and adjusted to a concentration of 2 million/ml in medium 199 with additives. Then, Lizak preparation was added to the cells and starch solution was used in control. Imupret and Esberitox preparations were added to the culture with or without Lizak preparation. After cultivation, the levels of proinflammatory cytokine – Interleukin-1β, pro-allergic factor – Interleukin-4, Th-1 – derivative of cytokine – interferon-γ were studied in the supernatant using the «Tsitokin LLC» reagent kits (RF), as well as tissue regeneration factor – transforming growth factor –TGF-1β (Austria). The preparation was prepared from the cell pellet, in which the relative nonviable cell count was determined in a sample with trypan blue using a light microscope (Olympus CX21FS1).The statistical analysis was performed using Student's t-distribution. Results: Plant-derived preparations did not have any effect on cell viability in culture, did not reduce the level of the pro-inflammatory cytokine interleukin-1β and did not stimulate the production of the regeneration factor TGF-1β. At the same time, the combined use of plant-derived preparations and the antibacterial preparation Lizak in cell culture of tonsils was accompanied by an increase in cell viability compared to the use of Lizak preparation separately, the stimulation of the regulatory antiviral factor interferon-γ and an increase in the production of tissue regeneration factor. Conclusion: The immunomodulating properties of the antibacterial preparation Lizak and plant-derived immunomodulator Esberitox significantly differ in the points of application. Both plant-derived preparations stimulated the production of γ-interferon by tonsil cells in the presence of Lizak preparation, the transforming growth factor TGF-1β, the viability of tonsil cells was the highest with the combination of Lizak and Esberitox.

scholarly journals Serum CYR61 Is Associated With Airway Inflammation and Is a Potential Biomarker for Severity in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhu-Xia Tan ◽  
Lin Fu ◽  
Wen-Jing Wang ◽  
Ping Zhan ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Inflammatory Cytokines ◽  
Pulmonary Inflammation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Tnf Α ◽  
High Level

Background: Cysteine-rich 61 (CYR61) and inflammation was upregulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, the association between CYR61 and inflammation was unclear in COPD patients. This study aimed to analyze the association of serum CYR61 with pulmonary inflammation and lung function indexes in COPD patients.Methods: One hundred and fifty COPD patients and 150 control subjects were enrolled. Serum and pulmonary CYR61 was detected. Lung function indexes were evaluated in COPD patients.Results: Serum CYR61 level was elevated and pulmonary CYR61 expression was upregulated in COPD patients. An increased CYR61 was associated with decreased pulmonary function indexes in COPD patients. Further analyses showed that nuclear factor-kappa B (NF-κB) p65-positive nuclei was elevated in the lungs of COPD patients with high level of CYR61. Accordingly, serum monocyte chemotactic protein (MCP)-1 and tumor necrosis factor α (TNF-α), two downstream inflammatory cytokines of NF-κB pathway, were increased in parallel with CYR61, among which serum MCP-1 and TNF-α were the highest in COPD patients with high level of CYR61. Moreover, a positive correlation, determined by multivariate regression that excluded the influence of age, gender and smoking, was observed between serum CYR61 and inflammatory cytokines in COPD patients.Conclusion: These results provide evidence that an increased CYR61 is associated with pulmonary inflammation and COPD progression. Inflammatory cytokines may be the mediators between CYR61 elevation and COPD progression.

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 Molecular and Cellular Mechanisms Responsible for Beneficial Effects of Mesenchymal Stem Cell-Derived Product “Exo-d-MAPPS” in Attenuation of Chronic Airway Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Carl Randall Harrell ◽  
Dragica Miloradovic ◽  
Ruxana Sadikot ◽  
Crissy Fellabaum ◽  
Bojana Simovic Markovic ◽  
...  
Keyword(s):  
Animal Model ◽  
Airway Inflammation ◽  
Natural Killer ◽  
Inflammatory Cytokines ◽  
Therapeutic Agent ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Cell Based Therapy ◽  
Copd Patients ◽  
Chronic Airway

Mesenchymal stem cells (MSCs), due to their potential for differentiation into alveolar epithelial cells and their immunosuppressive characteristics, are considered a new therapeutic agent in cell-based therapy of inflammatory lung disorders, including chronic obstructive pulmonary disease (COPD). Since most of the MSC-mediated beneficent effects were the consequence of their paracrine action, herewith, we investigated the effects of a newly designed MSC-derived product “Exosome-derived Multiple Allogeneic Protein Paracrine Signaling (Exo-d-MAPPS)” in the attenuation of chronic airway inflammation by using an animal model of COPD (induced by chronic exposure to cigarette smoke (CS)) and clinical data obtained from Exo-d-MAPPS-treated COPD patients. Exo-d-MAPPS contains a high concentration of immunomodulatory factors which are capable of attenuating chronic airway inflammation, including soluble TNF receptors I and II, IL-1 receptor antagonist, and soluble receptor for advanced glycation end products. Accordingly, Exo-d-MAPPS significantly improved respiratory function, downregulated serum levels of inflammatory cytokines (TNF-α, IL-1β, IL-12, and IFN-γ), increased serum concentration of immunosuppressive IL-10, and attenuated chronic airway inflammation in CS-exposed mice. The cellular makeup of the lungs revealed that Exo-d-MAPPS treatment attenuated the production of inflammatory cytokines in lung-infiltrated macrophages, neutrophils, and natural killer and natural killer T cells and alleviated the antigen-presenting properties of lung-infiltrated macrophages and dendritic cells (DCs). Additionally, Exo-d-MAPPS promoted the expansion of immunosuppressive IL-10-producing alternatively activated macrophages, regulatory DCs, and CD4+FoxP3+T regulatory cells in inflamed lungs which resulted in the attenuation of chronic airway inflammation. In a similar manner, as it was observed in an animal model, Exo-d-MAPPS treatment significantly improved the pulmonary status and quality of life of COPD patients. Importantly, Exo-d-MAPPS was well tolerated since none of the 30 COPD patients reported any adverse effects after Exo-d-MAPPS administration. In summing up, we believe that Exo-d-MAPPS could be considered a potentially new therapeutic agent in the treatment of chronic inflammatory lung diseases whose efficacy should be further explored in large clinical trials.

Inhibition of transforming growth factor-β/SMAD signalling by the interferon-γ/STAT pathway

Nature ◽  
10.1038/17826 ◽  
1999 ◽  
Vol 397 (6721) ◽  
pp. 710-713 ◽  
Author(s):  
Luis Ulloa ◽  
Jacqueline Doody ◽  
Joan Massagué
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interferon Γ ◽  
Stat Pathway
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