scholarly journals Andrographolide Inhibition of Th17-Regulated Cytokines and JAK1/STAT3 Signaling in OVA-Stimulated Asthma in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Qian Yu ◽  
YaJie Shi ◽  
Chang Shu ◽  
XuChun Ding ◽  
ShiPing Zhu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lung Tissue ◽  
Inflammatory Mediators ◽  
Airway Remodeling ◽  
Neutrophil Infiltration ◽  
Chronic Inflammatory Disease ◽  
Control Group ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Clinical Syndromes

Asthma has long been considered a disease of airway inflammation. The excessive or prolonged production of inflammatory mediators can result in airway remodeling and severe clinical syndromes such as dyspnea or even apnea. Therefore, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators in control of asthma. Novel therapeutics and mechanistic insight are sought for the management of this chronic inflammatory disease. Andrographolide (AG) is a type of diterpenoid ester compound and is reported to demonstrate multiple properties such as antioxidation and anti-inflammation. However, the anti-inflammatory capacity of AG by regulating immunologic function in airway of asthma has not been fully studied to date. Therefore, this study investigates whether AG is capable of suppressing the inflammatory response of asthma in OVA-stimulated mice and the mechanism by which this is achieved. Animals were randomly divided into 4 groups: control group, OVA model group, OVA + AG (0.1 mg/ml) group, and OVA + dimethylsulfoxide (DMSO) group. The serum, BALF, and lung tissue of the mice were collected separately for the administration of ELISA, rt-PCR, western blot and pathological section and staining. We found that AG attenuated the OVA-induced production of IL-6, IL-17A, IL-17F, and RORγt; inhibited the OVA-mediated phosphorylation of JAK 1 and STAT3; and alleviated airway remodeling and the neutrophil infiltration of lung tissue. We conclude that AG inhibits the inflammatory response of asthma in OVA-stimulated mice by blocking the activation of Th17-regulated cytokines and the JAK1/STAT3 signaling pathway.

scholarly journals Curcumin alone and in combination with augmentin protects against pulmonaryinflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice

2010 ◽  
Vol 59 (4) ◽  
pp. 429-437 ◽  
Author(s):  
Shruti Bansal ◽  
Sanjay Chhibber
Keyword(s):  
Klebsiella Pneumoniae ◽  
Mouse Model ◽  
Lung Tissue ◽  
Inflammatory Mediators ◽  
Bacterial Load ◽  
Neutrophil Infiltration ◽  
Lung Infection ◽  
Control Group ◽  
Intranasal Route ◽  
Anti Inflammatory

Acute lung injuries due to acute lung infections remain a major cause ofmortality. Thus a combination of an antibiotic and a compound with immunomodulatoryand anti-inflammatory activities can help to overcome acute lung infection-inducedinjuries. Curcumin derived from the rhizome of turmeric has been used fordecades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatoryproperties by downregulation of various inflammatory mediators. Keeping theseproperties in mind, we investigated the anti-inflammatory properties of curcuminin a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillationof bacteria in this mouse model of acute pneumonia-induced inflammation resultedin a significant increase in neutrophil infiltration in the lungs along withincreased production of various inflammatory mediators [i.e. malondialdehyde (MDA),myeloperoxidase (MPO), nitric oxide (NO), tumour necrosisfactor (TNF)-α] in the lung tissue. The animalsthat received curcumin alone orally or in combination with augmentin, 15 daysprior to bacterial instillation into the lungs via the intranasal route, showeda significant (P <0.05) decrease in neutrophil influxinto the lungs and a significant (P <0.05) decreasein the production of MDA, NO, MPO activity and TNF-α levels.Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-α levels significantly (P >0.05) as compared tothe control group. We therefore conclude that curcumin ameliorates lung inflammationinduced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereasaugmentin takes care of bacterial proliferation. Hence, curcumin can be usedas an adjunct therapy along with antibiotics as an anti-inflammatory or animmunomodulatory agent in the case of acute lung infection.

scholarly journals Dynamic evolution of emphysema and airway remodeling in two mouse models of COPD

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yue Yang ◽  
Tingting Di ◽  
Zixiao Zhang ◽  
Jiaxin Liu ◽  
Congli Fu ◽  
...  
Keyword(s):  
Lung Function ◽  
Mouse Models ◽  
Lung Tissue ◽  
Airway Remodeling ◽  
Exposed Group ◽  
The Body ◽  
Mouse Lung ◽  
Control Group ◽  
Suitable Model ◽  
Exposure Method

Abstract Background Establishment of a mouse model is important for investigating the mechanism of chronic obstructive pulmonary disease (COPD). In this study, we observed and compared the evolution of the pathology in two mouse models of COPD induced by cigarette smoke (CS) exposure alone or in combination with lipopolysaccharide (LPS). Methods One hundred eight wild-type C57BL/6 mice were equally divided into three groups: the (1) control group, (2) CS-exposed group (CS group), and (3) CS + LPS-exposed group (CS + LPS group). The body weight of the mice was recorded, and noninvasive lung function tests were performed monthly. Inflammation was evaluated by counting the number of inflammatory cells in bronchoalveolar lavage fluid and measuring the expression of the IL-6 mRNA in mouse lung tissue. Changes in pathology were assessed by performing hematoxylin and eosin and Masson staining of lung tissue sections. Results The two treatments induced emphysema and airway remodeling and decreased lung function. Emphysema was induced after 1 month of exposure to CS or CS + LPS, while airway remodeling was induced after 2 months of exposure to CS + LPS and 3 months of exposure to CS. Moreover, the mice in the CS + LPS group exhibited more severe inflammation and airway remodeling than the mice in the CS group, but the two treatments induced similar levels of emphysema. Conclusion Compared with the single CS exposure method, the CS + LPS exposure method is a more suitable model of COPD in airway remodeling research. Conversely, the CS exposure method is a more suitable model of COPD for emphysema research due to its simple operation.

scholarly journals MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3 signaling pathway

Oncotarget ◽  
2017 ◽  
Vol 8 (39) ◽  
pp. 65397-65406 ◽  
Author(s):  
Qiqi Zhang ◽  
Jia Su ◽  
Ziwei Wang ◽  
Hui Qi ◽  
Zeyong Ge ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats

2017 ◽  
Vol 67 (1) ◽  
pp. 125-135 ◽  
Author(s):  
Nouf M. Al-Rasheed ◽  
Laila Fadda ◽  
Hala A. Attia ◽  
Iman A. Sharaf ◽  
Azza M. Mohamed ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Lung Tissue ◽  
Inflammatory Mediators ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Control Group ◽  
Novel Therapy ◽  
Protein Expressions ◽  
Pre Treatment

AbstractThe study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.

scholarly journals Qufeng Xuanbi Formula ameliorates airway remodeling in asthmatic mice by suppressing airway smooth muscle cells proliferation through MEK/ERK signaling pathway

2021 ◽  
Author(s):  
Bohan Wang ◽  
Lingling Tang ◽  
Suofang Shi ◽  
Ying Yang ◽  
Xianhong Sun ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Tissue ◽  
Airway Remodeling ◽  
Erk Signaling ◽  
Immunofluorescent Staining ◽  
Control Group ◽  
Airway Smooth Muscle Cells ◽  
Therapeutic Effects ◽  
Protein Expressions

Abstract BackgroundAsthma is a common chronic respiratory disease. Qufeng Xuanbi Formula (QFXBF), a Chinese herbal decoction, has shown efficiency for the management of asthma. The purpose of current study is to investigate the potential therapeutic effects of QFXBF for the treatment of asthma both in vitro and in vivo. MethodsPDGF-induced ASMCs proliferation model and MTT assay have been applied for exploring the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, OVA group, High QFXBF group, Low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). The mouse allergic asthma model has been established by intranasally administered ovalbumin (OVA) sensitization method. Morphological changes of the lung tissue have been examined by hematoxylin and eosin (H&E) staining and Masson’s staining. Finally, the protein expressions of α-SMA, PCNA, p-MEK1/2, MEK1/2, p-ERK1/2, and ERK1/2 in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. ResultsPDGF induced significant increase in viability of ASMCs. Compared with mice in control group, the airway walls and airway smooth muscle of mice in OVA group mice thickened, and the inflammatory cells around the bronchus increased significantly. Moreover, administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathologic changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment of QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA and PCNA. ConclusionQFXBF can inhibit the proliferation of ASMCs via suppressing the MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.

Effect of miR-155 on Aplastic Anemia Rats Through Regulating Signal Transducer and Activator of Transcription 3 Signaling Pathway

2020 ◽  
Vol 10 (3) ◽  
pp. 397-401
Author(s):  
Qingxian Yan ◽  
Zhengjun Hou ◽  
Shuting Ye ◽  
Meiyun Su
Keyword(s):  
Aplastic Anemia ◽  
Signaling Pathway ◽  
Blood Cells ◽  
Mrna Level ◽  
White Blood Cells ◽  
Control Group ◽  
Stat3 Signaling ◽  
Group I ◽  
Stat3 Signaling Pathway ◽  
Experimental Group

Objective: To assess miR-155’s effect on aplastic anemia (AA) rats. Methods: In the present study, the healthy rats (control group) and AA rats including AA rats with miR-155 overexpression (experimental group I) and those with miR-155 deficiency (experimental group II), were selected. The levels of miR-155, STAT3 (a key gene in STAT3 signaling pathway) and phosphorylated STAT3 (p-STAT3) in control group and experimental group were detected via qPCR and Western blotting. Moreover, the number of white blood cells (WBCs), red blood cells (RBCs), platelets (PLTs) and hemoglobin (HGB) level were also measured. Results: The level of miR-155 in AA rats was significantly declined compared with that in healthy rats (p < 0.05). STAT3 mRNA level was significantly declined in AA rats with miR-155 overexpression compared with that in AA rats with miR-155 deficiency (p < 0.05). STAT3 and p-STAT3 protein expression in AA rats with miR-155 overexpression were significantly lower than those in AA rats with miR-155 deficiency (p < 0.05). Besides, it was found that the number of WBC, RBC, PLT and HGB level were significantly elevated in AA rats with miR-155 overexpression compared to those in AA rats with miR-155 deficiency (p < 0.05). Conclusion: miR-155 can improve the AA symptoms of rats through inhibiting the STAT3 signaling pathway.

scholarly journals Phytochemical-induced reduction of pulmonary inflammation during Klebsiella pneumoniae lung infection in mice

2014 ◽  
Vol 8 (07) ◽  
pp. 838-844 ◽  
Author(s):  
Shruti Bansal ◽  
Sanjay Chhibber
Keyword(s):  
Lung Tissue ◽  
Histopathological Examination ◽  
Curcuma Longa ◽  
Pulmonary Inflammation ◽  
Bacterial Load ◽  
Neutrophil Infiltration ◽  
Lung Infection ◽  
Control Group ◽  
Inflammatory Parameters ◽  
Anti Inflammatory

Introduction: Curcumin, a polyphenol derived from the herb Curcuma longa, has number of antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Its anti-inflammatory property was here studied alone and in combination with clarithromycin in a mouse model of acute inflammation. Methodology: A total of 80 mice divided into four groups were used. Mice receiving curcumin and/or clarithromycin were fed orally with curcumin (150 mg/kg/day) for 15 days prior to infection, whereas clarithromycin was administered orally (30 mg/kg/day) 12 hours post infection. Simultaneously, the control group receiving only infection but no treatment was also set up. Bacterial load estimation, histopathological examination and analysis of inflammatory parameters was performed on various days for all groups. Results: Intranasal inoculation of bacteria resulted in significant increase in neutrophil infiltration along with increased production of various inflammatory mediators (malondialdehyde, myeloperoxidase, nitric oxide, TNFα) in lung tissue. Clarithromycin treatment significantly decreased the bacterial load and other inflammatory components in infected mice, but animals receiving curcumin alone or in combination with clarithromycin showed a much more significant (p < 0.05) reduction in neutrophil influx along with reduced levels of various inflammatory parameters. Though treatment with curcumin did not reduce the bacterial load, in combination with clarithromycin, both bacterial proliferation and lung tissue damage were checked. Conclusions: Though clarithromycin, because of its associated side effects, may not be the preferred treatment, it can be used in conjunction with curcumin. The latter as an adjunct therapy will help to down regulate the exaggerated state of immune response during acute lung infection.

scholarly journals Punicalagin Exerts Protective Effects against Ankylosing Spondylitis by Regulating NF-κB-TH17/JAK2/STAT3 Signaling and Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xinzhe Feng ◽  
Qinyuan Yang ◽  
Chen Wang ◽  
Wenwen Tong ◽  
Weidong Xu
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ankylosing Spondylitis ◽  
Inflammatory Mediators ◽  
Antioxidant Status ◽  
Serum Levels ◽  
Protective Role ◽  
Chronic Inflammatory Disease ◽  
Protective Effects ◽  
Stat3 Signaling

Background. Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS. Methods. BALB/c mice induced spondylitis were sacrificed 24 h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2/STAT3 proteins and proteins of the nuclear factor-κB (NF-κB) pathway was determined by immunoblotting. Serum levels of inflammatory mediators—TNF-α, IL-1β, IL-6, IL-17A, and IL-23—were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes—catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)—was determined. Results. Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF-κB pathway and JAK2/STAT3 signaling were significantly (p<0.05) downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL-17A/IL-23 axis. Conclusion. The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF-κB/TH17/JAK2/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.

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