scholarly journals Cavidine protects against asthma in neonatal asthmatic mice model by attenuating PI3Ks/NF-κB signaling pathway

2021 ◽  
Vol 18 (3) ◽  
pp. 513-518
Author(s):  
Qin Hao ◽  
Juan Shen ◽  
Lin Zhao
Keyword(s):  
Signaling Pathway ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Mice Model ◽  
Altered Expression ◽  
Neonatal Mice ◽  
Cytokine Levels ◽  
Asthmatic Group

Purpose: To evaluate the protective effect of cavidine against asthma in neonatal mice. Methods: Neonatal mice were treated with cavidine at doses of 5 and 10 mg/kg, po, 2 h prior to asthma induction with ovalbumin (OVA) on the 1st and 14th days of the treatment protocol. The anti-asthma activity of cavidine was evaluated by determining the number of inflammatory cells and cytokine levels in broncho-alveolar lavage fluid (BALF) and OVA-specific IgE and TGF-β 1 in the serum of OVAsensitized mice. The levels of NF-ƙB and PI3K protein expression were determined in the lung tissues of OVA-sensitized mice. Results: Cavidine attenuated the number of inflammatory cells and cytokines in BALF of OVAsensitized mice. The levels of OVA-specific IgE and TGF-β 1 decreased significantly in cavidine-treated groups, when compared to asthmatic group of mice, while NF-ƙB was significantly downregulated (p < 0.01). The altered expression of PI3K signaling protein was attenuated in the lung tissues of cavidinetreated mice sensitized with OVA. Conclusion: These results reveal that the anti-asthma effect of cavidine in OVA-induced asthmatic neonatal mice occurs via reduction of inflammation and immune responsive cells linked to PI3Ks/ NF-κB signaling pathway in lung tissues. These findings suggest that cavidine may be clinically suitable for the management of asthma.

scholarly journals MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1202-1212
Author(s):  
Aichun Zhang ◽  
Yangzi Jin
Keyword(s):  
Allergic Rhinitis ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Inflammatory Factors ◽  
Pcr Analysis ◽  
Reverse Transcription Pcr ◽  
Pathway Activation ◽  
Nasal Lavage Fluid

AbstractAllergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.

scholarly journals Allergic Inflammation Caused by Dimerized Translationally Controlled Tumor Protein is Attenuated by Cardamonin

2021 ◽  
Vol 12 ◽  
Author(s):  
Haejun Pyun ◽  
Joo-Won Nam ◽  
Hyunsoo Cho ◽  
Jiyoung Park ◽  
Eun Kyoung Seo ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Allergic Inflammation ◽  
Inflammatory Cells ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Translationally Controlled Tumor Protein ◽  
Dimeric Form ◽  
Allergic Mouse ◽  
Inflammatory Effect

We demonstrated in our previous reports that dimeric form of translationally controlled tumor protein (dTCTP) initiates a variety of allergic phenomena. In the present study, we examined whether and how dTCTP’s role in allergic inflammation can be modulated or negated. The possible potential of cardamonin as an anti-allergic agent was assessed by ELISA using BEAS-2B cells and OVA-challenged allergic mouse model. The interaction between cardamonin and dTCTP was confirmed by SPR assay. Cardamonin was found to reduce the secretion of IL-8 caused by dTCTP in BEAS-2B cells by interacting with dTCTP. This interaction between dTCTP and cardamonin was confirmed through kinetic analysis (KD = 4.72 ± 0.07 μM). Also, cardamonin reduced the migration of various inflammatory cells in the bronchoalveolar lavage fluid (BALF), inhibited OVA specific IgE secretion and bronchial remodeling. In addition, cardamonin was observed to have an anti-allergic response by inhibiting the activity of NF-κB. Cardamonin exerts anti-allergic anti-inflammatory effect by inhibiting dTCTP, suggesting that it may be useful in the therapy of allergic diseases.

scholarly journals The growth factor/ cytokine midkine may participate to cytokine storm and contribute to the pathogenesis of SARS-CoV-2 infected patients

2021 ◽  
Author(s):  
Sema Ketenci ◽  
Şükrü Aynacıoğlu
Keyword(s):  
Tissue Repair ◽  
Inflammatory Diseases ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Clinical Situation ◽  
Lung Damage ◽  
Cytokine Storm ◽  
Hypoxic Conditions ◽  
Cytokine Levels ◽  
Important Cytokine

The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, China and has rapidly become global challenges, creating major challenges to health systems in almost every country in the world it has turned into a pandemic. COVID-19 poses a risky clinical situation that can range from mild illness to severe respiratory failure requiring admission to intensive care. It is known to cause cytokine storm in some critically ill patients. However, more and more evidence showed that there is a dramatic increase in cytokine levels in patients diagnosed with COVID-19. Midkine (MK) is involved in various physiological and pathological processes, which some of them are desired and beneficial such as controlling tissue repair and antimicrobial effects, but some others are harmful such as promoting inflammation, carcinogenesis and chemo-resistance. Also, MK is expressed in inflammatory cells and released by endothelial cells under hypoxic conditions. Considering all this information, there are strong data that MK, an important cytokine known to increase in inflammatory diseases, may overexpressed in patients who are positive for COVID-19. The overexpression of MK reveals a picture leading to fibrosis in the lung damage. Therefore, questions arise about how the concentration of MK changes in CoVID-19 patients and can we use it as an inflammation biomarker or in the treatment protocol in the future.

YiQiFuMai Lyophilized Injection Attenuates Sepsis-Induced Acute Lung Injury via TLR4/Src/VE-cadherin/p120-catenin Signaling Pathway

2020 ◽  
Author(s):  
Xue-wei Pan ◽  
Li-xuan Xue ◽  
Qian-liu Zhou ◽  
Jia-zhi Zhang ◽  
Yu-jie Dai ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Cecal Ligation ◽  
Inflammatory Cells ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Lung Edema ◽  
P120 Catenin

Abstract Background: Sepsis is a severe disorder leading to a clinically critical syndrome of multiple organ dysfunction syndrome. Most patients with sepsis will be associated with acute lung injury (ALI), which is an independent risk factors of organ failure and death in patients with sepsis at the same time. YiQiFuMai Lyophilized Injection (YQFM) is a modern traditional Chinese prescription preparation, which could ameliorate ALI induced by lipopolysaccharide (LPS) or fine particulate matter. The current study aimed to investigate the effect of YQFM on sepsis-induced ALI and the underlying mechanism.Methods: Male C57BL/6J mice were treated with cecal ligation and puncture (CLP) after tail intravenous injected with YQFM (1, 2 and 4 g/kg). The measurements of lung edema, evans blue leakage, myeloperoxidase content, inflammatory cells in bronchoalveolar lavage fluid, histopathological assay and expression of associated proteins were performed at 18 h after CLP.Results: The results illustrated that YQFM inhibited pulmonary edema and inflammatory response, thus ameliorated ALI in sepsis mice. Furthermore, the expression of TLR4 and phosphorylated Src was down-regulated, and the expression of p120-catenin and VE-cadherin was restored by YQFM administration.Conclusion: Our study suggested the therapeutic potential of YQFM on treating sepsis-induced ALI via regulating TLR4/Src/VE-cadherin/p120-catenin signaling pathway.

scholarly journals Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoying Huang ◽  
Jiangfeng Tang ◽  
Hui Cai ◽  
Yi Pan ◽  
Yicheng He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Interleukin 1 ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Therapeutic Mechanism

The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.

scholarly journals Effects of caffeoylxanthiazonoside on airway inflammation in an allergic asthma mice model

2021 ◽  
Vol 18 (4) ◽  
pp. 761-766
Author(s):  
Qian Wu ◽  
Hui Wang ◽  
Xiaowen Che ◽  
Wei Wang
Keyword(s):  
Protein Expression ◽  
Western Blot ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Ifn Γ

Purpose: To investigate the inhibitory effects of caffeoylxanthiazonoside (CYT) on airway inflammation in mice and its mechanism of action. Methods: An allergic asthma mice model was established by intraperitoneal injection and aerosol nebulization with ovalbumin (OVA). After treatment with CYT, the blood and bronchoalveolar lavage fluid (BALF) were collected from the mice. The leukocytes were classified and counted with Giemsa solution. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum levels of IgE, and IL-4, IL-5, IL-13 and IFN-γ in the BALF of mice. Lung tissues were obtained from the mice and MUC5AC protein expression was measured by western blot. Results: CYT significantly decreased the serum level of IgE in asthmatic mice. Inflammatory cells in BALF of mice were markedly reduced (p < 0.05) by CYT treatment at varying doses (10, 20, and 40 mg/kg). Treatment with CYT also significantly suppressed the cytokines of IL-4, IL-5 and IL-13 and increased the IFN-γ in the BLAF of OVA-induced allergic asthma mice (p < 0.05). Western blot results indicate that CYT treatment significantly decreased the expression of MUC5AC protein in the lung tissues of asthmatic mice. In addition, no significant effects on the body weight of the mice were found after CYT treatment. Conclusion: Caffeoylxanthiazonoside inhibits airway inflammation in allergic asthma mice by altering Th1/Th2 via re-balancing of related cytokines and downregulation of lung MUC5AC protein expression. Therefore, this compound can potentially be developed for the therapeutic management of inflammation in allergic asthma.

scholarly journals The growth factor/cytokine midkine may participate in cytokine storm and contribute to the pathogenesis of severe acute respiratory syndrome coronavirus 2-infected patients

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Sema Ketenci ◽  
A. Şükrü Aynacıoğlu
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Diseases ◽  
Treatment Protocol ◽  
Inflammatory Cells ◽  
Clinical Situation ◽  
Main Body ◽  
Cytokine Storm ◽  
Global Challenge ◽  
Hypoxic Conditions ◽  
Cytokine Levels

Abstract Background The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, China, and has rapidly become a global challenge, creating major challenges to health systems in almost every country in the world it has turned into a pandemic. COVID-19 poses a risky clinical situation that can range from mild illness to severe respiratory failure, requiring admission to intensive care. Main body It is known that SARS-CoV-2 infection causes a cytokine storm in some critically ill patients. However, more and more evidence showed that there is a dramatic increase in cytokine levels in patients diagnosed with COVID-19. Midkine (MK) is involved in various physiological and pathological processes, which some of them are desired and beneficial such as controlling tissue repair and antimicrobial effects, but some others are harmful such as promoting inflammation, carcinogenesis, and chemoresistance. Also, MK is expressed in inflammatory cells and released by endothelial cells under hypoxic conditions. Conclusions Considering all this information, there are strong data that midkine, an important cytokine known to increase in inflammatory diseases, may be overexpressed in patients who are positive for COVID-19. The overexpression of MK reveals a picture leading to fibrosis and damage in the lung. Therefore, questions arise about how the expression  of  MK  changes in COVID-19 patients and can we use it as an inflammation biomarker or in the treatment protocol in the future.

Overexpression of immune-responsive gene 1 prevents acute otitis media due to streptococcus pneumoniae infection through Nrf2- Hmox1 pathway

2019 ◽  
Author(s):  
Peizhen Yang ◽  
Yufen Li ◽  
Dongqing Wang ◽  
Zhipeng Chen
Keyword(s):  
Streptococcus Pneumoniae ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Lavage Fluid ◽  
Mice Model ◽  
Nrf2 Signaling Pathway ◽  
Positive Rate

Abstract Background: Acute otitis media (AOM) is one of the most commonly diagnosed childhood diseases that are associated with influenza infection. Immunoresponsive gene 1 (Irg1) is overexpressed in mammalian macrophage during inflammation process. Here, the present study aims to investigate the role of Irg1 in streptococcus pneumoniae infection-induced inflammatory response in AOM through Nrf2 signaling pathway. Methods: Positive rate of streptococcus pneumoniae and expression of Irg1, Nrf2 and Hmox1 were determined in the middle ear lavage fluid from 85 AOM patients infected with streptococcus pneumoniae and 48 healthy subjects. After the successful establishment of mice model with AOM, macrophage was harvest from the middle ear lavage fluid of mice. At last, to investigate the effect of Irg1 and Nrf2 signaling pathway on inflammatory response and streptococcus pneumoniae infection by accumulating macrophage, Irg1, sh-Irg1 and retinoic acid (an inhibitor of Nrf2 signaling pathway) were injected into AOM mice. Results: Irg1 exhibited a high level and activated Nrf2 signaling pathway was detected in AOM. Besides, positive rate of streptococcus pneumoniae was increased in AOM. Furthermore, in the mice model with AOM, Irg1 could repress inflammatory response by downregulating expression of TNF-α, IL-6 and IL-1β and inhibit streptococcus pneumoniae infection by stimulating accumulation of macrophage to increase its endocytosis through activation of Nrf2 signaling pathway. Conclusion: Taken together, Irg1 contributes to inhibiting inflammatory response and streptococcus pneumoniae infection in AOM by promoting accumulation of macrophage through activation of Nrf2 signaling pathway, which provides novel therapeutic targets for AOM therapy.

Mepacrine inhibits subepithelial fibrosis by reducing the expression of arginase and TGF-β1 in an extended subacute mouse model of allergic asthma

2009 ◽  
Vol 297 (3) ◽  
pp. L411-L419 ◽  
Author(s):  
Ulaganathan Mabalirajan ◽  
Jyotirmoi Aich ◽  
Anurag Agrawal ◽  
Balaram Ghosh
Keyword(s):  
Airway Inflammation ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Allergen Challenge ◽  
Inflammatory Cells ◽  
Transforming Growth Factor Β ◽  
Specific Ige ◽  
Mice Model ◽  
Crucial Component ◽  
Subepithelial Fibrosis

Asthma is a dynamic disorder of airway inflammation and airway remodeling with an imbalance in T helper type 1 (Th1)/Th2 immune response. Increased Th2 cytokines such as IL-4 and IL-13 induce arginase either directly or indirectly through transforming growth factor-β1 (TGF-β1) and lead to subepithelial fibrosis, which is a crucial component of airway remodeling. Synthetic antimalarials have been reported to have immunomodulatory properties. Mepacrine is known for its reduction of airway inflammation in short-term allergen challenge model by reducing Th2 cytokines and cysteinyl leukotrienes, which has an important role in the development of airway remodeling features. Therefore, we hypothesized that mepacrine may reduce airway remodeling. For this, extended subacute ovalbumin mice model of asthma was developed; these mice showed an increased expression of profibrotic mediators, subepithelial fibrosis, and goblet cell metaplasia along with airway inflammation, increased Th2 cytokines, allergen-specific IgE, IgG1, increased cytosolic PLA2 (cPLA2), and airway hyperresponsiveness. Presence of intraepithelial eosinophils and significant TGF-β1 expression in subepithelial mesenchymal regions by repeated allergen exposures indicate that asthmatic mice of this study have developed human mimicking as well as late stages of asthma. However, mepacrine treatment decreased Th2 cytokines and subepithelial fibrosis and alleviated asthma features. These reductions by mepacrine were associated with a decrease in levels and expression of TGF-β1 and the reduction in activity, expression of arginase in lung cytosol, and immunolocalization in inflammatory cells present in perivascular and peribronchial regions. These results suggest that mepacrine might reduce the development of subepithelial fibrosis by reducing the arginase and TGF-β1. These effects of mepacrine likely underlie its antiairway remodeling action in asthma.

scholarly journals Functional and pathological effects of prolonged hyperoxia in neonatal mice

1998 ◽  
Vol 275 (1) ◽  
pp. L110-L117 ◽  
Author(s):  
Barbara B. Warner ◽  
Lorie A. Stuart ◽  
Richard A. Papes ◽  
Jonathan R. Wispé
Keyword(s):  
Cell Proliferation ◽  
Lung Tissue ◽  
Prolonged Exposure ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Functional Changes ◽  
Neonatal Mice ◽  
Fluid Analysis ◽  
Neonatal Hyperoxia

Bronchopulmonary dysplasia (BPD) commonly develops in premature infants. An improved understanding of the pathophysiology of BPD requires better models. In this study, neonatal FVB/N mice were exposed to room air or 85% oxygen for 28 days. Neonatal hyperoxia resulted in decreased alveolar septation, increased terminal air space size, and increased lung fibrosis. These changes were evident after 7 days and more pronounced by 28 days. Decreased alveolarization was preceded by decreased proliferation of lung cells. After 3 days of hyperoxia, cell proliferation was decreased compared with room air littermates. Cell proliferation continued to be decreased in the first 2 wk but normalized by 4 wk. Hyperoxia caused an increased number of inflammatory cells in lung tissue and in lung lavage fluid. Analysis of lung tissue RNA by RT-PCR showed that hyperoxia increased expression of the proinflammatory cytokines interleukin-1α and macrophage inflammatory protein-1α. Prolonged neonatal hyperoxia caused functional changes, decreasing lung volume and pulmonary compliance. We conclude that prolonged exposure of neonatal mice to hyperoxia creates a lesion that is very similar to human BPD and suggests that altered cell proliferation may be important in the pathogenesis of chronic neonatal lung disease.

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