scholarly journals Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κ Signaling Pathway to Alleviate Airway hyperresponsiveness in OVA Mice

2021 ◽  
Author(s):  
Qirui Duan ◽  
Dong Yang ◽  
Juan Zhi
Keyword(s):  
Signaling Pathway ◽  
Airway Hyperresponsiveness ◽  
Airway Resistance ◽  
Airway Hyperreactivity ◽  
Blank Group ◽  
Lung Protection ◽  
Protein Levels ◽  
Asthma Model ◽  
Group A ◽  
Asthma Group

Abstract Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. RESULTS: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

scholarly journals Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κB Signaling Pathway to Alleviate Airway Hyperresponsiveness in OVA Mice

2021 ◽  
Author(s):  
Juan Zhi ◽  
Qirui Duan ◽  
Qian yu Wang ◽  
Xiyu Du ◽  
Dong Yang
Keyword(s):  
Signaling Pathway ◽  
Airway Hyperresponsiveness ◽  
Airway Resistance ◽  
Airway Hyperreactivity ◽  
Blank Group ◽  
Lung Protection ◽  
Protein Levels ◽  
Asthma Model ◽  
Group A ◽  
Asthma Group

Abstract Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. Results: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

scholarly journals Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κB Signaling Pathway to Alleviate Airway Hyperresponsiveness in OVA Mice

2021 ◽  
Author(s):  
Juan Zhi ◽  
Qirui Duan ◽  
Qian yu Wang ◽  
Xiyu Du ◽  
Dong Yang
Keyword(s):  
Signaling Pathway ◽  
Airway Hyperresponsiveness ◽  
Airway Resistance ◽  
Airway Hyperreactivity ◽  
Blank Group ◽  
Lung Protection ◽  
Protein Levels ◽  
Asthma Model ◽  
Group A ◽  
Asthma Group

Abstract Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. Results: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

Effects of Dapagliflozin on Renal Interstitial Fibrosis in Diabetic Rats through Smad3, TIMP1 and MMP24 Pathway

2021 ◽  
Vol 7 (4) ◽  
pp. 690-696
Author(s):  
Yueyao Chen ◽  
Haixiang Li ◽  
Chaoqin Chen
Keyword(s):  
Interstitial Fibrosis ◽  
Intervention Group ◽  
Kidney Tissue ◽  
Diabetic Rats ◽  
Renal Interstitial Fibrosis ◽  
Blank Group ◽  
Protein Levels ◽  
Group A ◽  
Group 3 ◽  
Group 2

Objective: This research was designed to probe into the effects of Dapagliflozin on renal interstitial fibrosis in diabetic rats through Smad3, TIMP1 and MMP24 pathway. Methods: Rats were bought to establish models, and then intervened by Dapagliflozin. Human mesangial cell lines (HMCs) stimulated by high glucose were purchased, and the Smad3, TIMP1 and MMP24 levels in rats after modeling and Dapagliflozin intervention were detected. The Smad3, TIMP1 and MMP24 protein expression in kidney tissue was examined after the rats were killed, and the expression in an intervention group (IG) and a blank group (BG) were analyzed. The cells were divided into three groups: Dapagliflozin intervention (Group 1), TGF-P1/Smad3 pathway inhibitor SIS3 intervention (Group 2) and no intervention (Group 3). The TIMP1 and MMP24 levels were assessed. Results: The Smad3 and MMP24 levels in group A were higher than those in other two groups (p < 0.05), while those of TIMP1 were lower (p < 0.05). Compared with pre-intervention, the Smad3 and MMP24 levels in groups A and B decreased (p < 0.05), while those of TIMP1 increased (p < 0.05). The Smad3 and MMP24 protein levels in groups A and B were higher than those in other two groups (p < 0.05), while those of TIMP1 was lower (p < 0.05). Compared with the BG, the Smad3 and MMP24 expression in the IG was lower (p < 0.05) and that of TIMP1 was higher (p < 0.05). The TIMP1 expression in Group 3 was lower (p < 0.05) and that of MMP24 was higher than those in Groups 1 and 2 (p < 0.05). Conclusion: Dapagliflozin can treat diabetic renal interstitial fibrosis by inhibiting TGF-P1/Smad3 signaling pathway, decreasing MMP24 and increasing TIMP1.

scholarly journals Transtracheal Instillation of Anti-TSLP Antibody Alleviates Airway Inflammation and Airway Hyperresponsiveness in OVA-Induced Asthma Model Mice

2021 ◽  
Author(s):  
Xiaowen Chen ◽  
Xiangfeng Fang ◽  
Jiang Qian ◽  
Jinle Lin ◽  
DongFeng Li ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Animal Studies ◽  
Histopathological Examination ◽  
Allergic Inflammation ◽  
Inflammatory Cells ◽  
Control Group ◽  
Model Group ◽  
Protein Levels ◽  
Asthma Model

Abstract BackgroundThymic stromal lymphopoietin (TSLP) is a mainly epithelial cell-derived cytokine that may be important in initiating T2 allergic inflammation. Anti-TSLP antibody inhibit allergic inflammation. Previous animal studies have evaluated the anti-allergic efficacy of injecting anti-TSLP antibody intraperitoneally, subcutaneously, or intravenously. However, transtracheal instillation, a less invasive route for anti-TSLP antibody administration, is hitherto unstudied. This study evaluates the efficacy of transtracheally instilling anti-TSLP antibody in inhibiting airway inflammation and hyperresponsiveness in OVA-induced asthma model Balb/c mice.MethodsBalb/c mice were randomly divided into four groups: the control group, the OVA-induced asthma model group, the anti-TSLP mAb treatment group (TSLP mAb group), and the IgG2a mAb control group (IgG2a mAb group). Each group contained nine to eleven mice. Mice in the asthma model group were sensitized with OVA to trigger allergic responses and were treated with transtracheal instillation of normal saline. Mice in the TSLP mAb group received transtracheal instillation of anti-TSLP mAb, while mice in the IgG2a group received transtracheal instillation of IgG2a mAb. Both of these groups were then subjected to OVA challenge. Airway responsiveness was measured as an enhanced pause (Penh) using noninvasive plethysmography. The severity of inflammation was evaluated by histopathological examination using the Underwood assessment of the lung sections. Changes in expression of TSLP, TSLP receptor (TSLPR), T-box transcription factor (T-bet), GATA binding protein 3 (GATA3) and forkhead box protein P3 (Foxp3) were assessed using RT-PCR and immunohistochemical staining. ResultsAirway hyperresponsiveness and infiltration of airway inflammatory cells in the TSLP mAb group were significantly reduced, compared with the OVA and the IgG2a mAb groups. Meanwhile，TSLP, GATA3 mRNA expression and GATA3 protein levels were significantly decreased in the TSLP mAb group, compared with the OVA and the IgG2a mAb groups (P＜0.05）. No significant differences were observed in either T-bet or Foxp3 in the lung section of mRNA and protein expression among these four groups (P＞0.05).ConclusionTranstracheal instillation of anti-TSLP antibody attenuated lung inflammation and airway hyperresponsiveness in OVA-induced asthmatic mice, possibly through downregulation of perivascular and peribronchiolar lymphocytes, neutrophils and GATA3 expression in the airway.

scholarly journals Altered Frequency of NK Cells and Treg Cells by Astragalus Polysaccharide Combined with Budesonide in Asthma Model Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Wei Zhang ◽  
Kuifen Ma
Keyword(s):  
Nk Cells ◽  
Bronchial Asthma ◽  
Airway Resistance ◽  
Treg Cells ◽  
The Other ◽  
Control Group ◽  
Rt Pcr ◽  
Protein Levels ◽  
Asthma Model ◽  
Astragalus Polysaccharide

Objective. We investigated the efficacy of astragalus polysaccharide (APS) combined with budesonide and the effect on expressions of peripheral NK cells and Treg cells and the molecular mechanism in mice with bronchial asthma. Methods. In this study, we established a mouse model of asthma. Four groups of BaLB/C mice were developed; control group had no asthma induction, and the other three groups of mice were sensitized by OVA (Ovalbumin), OVA + budesonide, and OVA + APS + budesonide. Flow cytometry was used to determine the proportion of NK cells and Treg cells. Levels of cytokines IL-4 and IL-10 were detected using RT-PCR and ELISA. Results. Asthma mice treated with APS + budesonide showed alleviated airway resistance compared to model mice (P<0.05). The percentage of dendritic cells (DCs) was reduced (P<0.05), while anti-inflammatory NK cells and Treg cells significantly increased after APS + budesonide treatment (P<0.05). Further, APS + budesonide treatment resulted in improvements in IL-4 and IL-10 mRNA and protein levels (P<0.05). Conclusion. APS combined with budesonide medication may regulate expressions of DCs cells and related cytokines, reliving clinical symptom of bronchial asthma.

scholarly journals Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 341 ◽  
Author(s):  
Hyun-Su Lee ◽  
Gil-Saeng Jeong
Keyword(s):  
Signaling Pathway ◽  
Neurodegenerative Disorders ◽  
Nuclear Translocation ◽  
Protoporphyrin Ix ◽  
Protective Role ◽  
Osteoclast Formation ◽  
Protective Effects ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Pre Treatment

Since hypoxia-induced neurotoxicity is one of the major causes of neurodegenerative disorders, including the Alzheimer’s disease, continuous efforts to find a novel antioxidant from natural products are required for public health. 6,7,4′-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been shown to inhibit osteoclast formation and have an antibacterial activity. However, no evidence has reported whether THF has a protective role against hypoxia-induced neurotoxicity. In this study, we found that THF is not cytotoxic, but pre-treatment with THF has a cytoprotective effect on CoCl2-induced hypoxia by restoring the expression of anti-apoptotic proteins in SH-SY5y cells. In addition, pre-treatment with THF suppressed CoCl2-induced hypoxia-related genes including HIF1α, p53, VEGF, and GLUT1 at the mRNA and protein levels. Pre-treatment with THF also attenuated the oxidative stress occurred by CoCl2-induced hypoxia by preserving antioxidant proteins, including SOD and CAT. We revealed that treatment with THF promotes HO-1 expression through Nrf2 nuclear translocation. An inhibitor assay using tin protoporphyrin IX (SnPP) confirmed that the enhancement of HO-1 by pre-treatment with THF protects SH-SY5y cells from CoCl2-induced neurotoxicity under hypoxic conditions. Our results demonstrate the advantageous effects of THF against hypoxia-induced neurotoxicity through the HO-1/Nrf2 signaling pathway and provide a therapeutic insight for neurodegenerative disorders.

scholarly journals Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Hee-Soo Han ◽  
Eungyeong Jang ◽  
Ji-Sun Shin ◽  
Kyung-Soo Inn ◽  
Jang-Hoon Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Molecular Data ◽  
Mrna Levels ◽  
Protein Levels ◽  
Stat3 Phosphorylation ◽  
Stat Signaling ◽  
Cox 2 ◽  
Anti Inflammatory

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

scholarly journals (Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose

2015 ◽  
Vol 309 (3) ◽  
pp. E302-E310 ◽  
Author(s):  
Caixia Li ◽  
Helmy M. Siragy
Keyword(s):  
Signaling Pathway ◽  
High Glucose ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Autophagic Flux ◽  
Bafilomycin A1 ◽  
Mtor Signaling Pathway ◽  
Autophagosome Formation ◽  
Podocyte Injury ◽  
Protein Levels

High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62. In contrast, high glucose decreased activation of UNC-51-like kinase-1 (ULK1) by phosphorylating Ser757 and protein levels of microtubule-associated protein-1 light chain 3B (LC3B)-II and Lamp-2. Bafilomycin A1 increased LC3BII and p62 accumulation in high-glucose-treated cells. High glucose reduced the autophagic flux. Confocal microscopy studies showed significant reduction in the protein level of LC3B in response to high glucose. Cyto-ID autophagy staining showed a significant decrease in autophagosome formation with high glucose. In the absence of PRR, activation of Akt with sc-79 or mTOR with MHY-1485 increased p62 accumulation. Caspase-3/7 activity and apoptosis monitored by TUNEL assay were significantly increased in podocytes treated with high glucose. PRR siRNA significantly reversed the effects of high glucose. Based on these data, we conclude that high glucose decreases autophagy and increases apoptosis in mouse podocytes through the PRR/PI3K/Akt/mTOR signaling pathway.

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