scholarly journals Hypoxia potentiates allergen induction of HIF-1α, chemokines, airway inflammation, TGF-β1, and airway remodeling in a mouse model

2013 ◽  
Vol 147 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Kwang Je Baek ◽  
Jae Youn Cho ◽  
Peter Rosenthal ◽  
Laura E. Crotty Alexander ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Tgf Β1

scholarly journals Proanthocyanidin from Grape Seed Extract Inhibits Airway Inflammation and Remodeling in a Murine Model of Chronic Asthma

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Dan-Yang Zhou ◽  
Su-Rong Fang ◽  
Chun-Fang Zou ◽  
Qian Zhang ◽  
Wei Gu
Keyword(s):  
Growth Factor ◽  
Airway Inflammation ◽  
Murine Model ◽  
Transforming Growth Factor ◽  
Immunoglobulin E ◽  
Airway Remodeling ◽  
Grape Seed ◽  
Total Serum ◽  
Chronic Asthma ◽  
Tgf Β1

Asthma is characterized by airway inflammation and airway remodeling. Our previous study revealed that grape seed proanthocyanidin extract (GSPE) could inhibit asthmatic airway inflammation and airway hyper-responsiveness by down-regulation of inducible nitric oxide synthase in a murine model of acute asthma. The present study aimed to evaluate GSPE's effects on airway inflammation and airway remodeling in a chronic asthmatic model. BALB/c mice were sensitized with ovalbumin (OVA) and then were challenged three times a week for 8 weeks. Airway responsiveness was measured at 24 h after the last OVA challenge. HE staining, PAS staining, and Masson staining were used to observe any airway inflammation in the lung tissue, airway mucus secretion, and subepithelial fibrosis, respectively. The cytokines levels in the lavage fluid (BALF) in addition to the total serum immunoglobulin E (IgE) levels were detected by ELISA. Furthermore, lung collagen contents, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) expression in the airway were assessed by hydroxyproline assay, immunohistochemistry, andWestern blot analysis, respectively. GSPE administration significantly suppressed airway resistance as well as reduced the amount of inflammatory cells, especially the eosinophil count, in BALF. Additionally, the GSPE treatment markedly decreased interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) levels in BALF in addition to the total serum IgE levels. A histological examination demonstrated that GSPE significantly ameliorated allergen-induced lung eosinophilic inflammation and decreased PAS-positive epithelial cells in the airway. The elevated hydroxyproline contents, lung α-SMA contents, and TGF-β1 protein expression that were observed in the OVA mice were also inhibited by GSPE. In conclusion, GSPE could inhibit airway inflammation and airway remodeling in a murine model of chronic asthma, thus providing a potential treatment for asthma.

scholarly journals Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma

2019 ◽  
Vol 316 (5) ◽  
pp. L843-L868 ◽  
Author(s):  
Jon M. Evasovic ◽  
Cherie A. Singer
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Severe Asthma ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
High Dose ◽  
Persistent Symptoms ◽  
Immune Factors ◽  
Tgf Β1

Severe asthma develops as a result of heightened, persistent symptoms that generally coincide with pronounced neutrophilic airway inflammation. In individuals with severe asthma, symptoms are poorly controlled by high-dose inhaled glucocorticoids and often lead to elevated morbidity and mortality rates that underscore the necessity for novel drug target identification that overcomes limitations in disease management. Many incidences of severe asthma are mechanistically associated with T helper 17 (TH17) cell-derived cytokines and immune factors that mediate neutrophilic influx to the airways. TH17-secreted interleukin-17A (IL-17A) is an independent risk factor for severe asthma that impacts airway smooth muscle (ASM) remodeling. TH17-derived cytokines and diverse immune mediators further interact with structural cells of the airway to induce pathophysiological processes that impact ASM functionality. Transforming growth factor-β1 (TGF-β1) is a pivotal mediator involved in airway remodeling that correlates with enhanced TH17 activity in individuals with severe asthma and is essential to TH17 differentiation and IL-17A production. IL-17A can also reciprocally enhance activation of TGF-β1 signaling pathways, whereas combined TH1/TH17 or TH2/TH17 immune responses may additively impact asthma severity. This review seeks to provide a comprehensive summary of cytokine-driven T cell fate determination and TH17-mediated airway inflammation. It will further review the evidence demonstrating the extent to which IL-17A interacts with various immune factors, specifically TGF-β1, to contribute to ASM remodeling and altered function in TH17-driven endotypes of severe asthma.

PPARγ Agonist PGZ Attenuates OVA-Induced Airway Inflammation and Airway Remodeling via RGS4 Signaling in Mouse Model

Inflammation ◽  
2018 ◽  
Vol 41 (6) ◽  
pp. 2079-2089 ◽  
Author(s):  
Xia Meng ◽  
Xinrong Sun ◽  
Yonghong Zhang ◽  
Hongyang Shi ◽  
Wenjing Deng ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Pparγ Agonist

Sevoflurane Prevents Airway Remodeling via Downregulation of VEGF and TGF-β1 in Mice with OVA-Induced Chronic Airway Inflammation

Inflammation ◽  
2019 ◽  
Vol 42 (3) ◽  
pp. 1015-1022 ◽  
Author(s):  
Qi-Ying Shen ◽  
Ling Wu ◽  
Chuan-Sheng Wei ◽  
Yan-Nan Zhou ◽  
Hui-Mei Wu
Keyword(s):  
Airway Inflammation ◽  
Airway Remodeling ◽  
Tgf Β1 ◽  
Chronic Airway

scholarly journals Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Liyang Dong ◽  
Ying Wang ◽  
Tingting Zheng ◽  
Yanan Pu ◽  
Yongbin Ma ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Airway Remodeling ◽  
Periodic Acid ◽  
Allergic Airway Inflammation ◽  
Lung Fibroblasts ◽  
Human Umbilical Cord ◽  
Chronic Asthma ◽  
Tgf Β1

Abstract Background As one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown. Methods BALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated. Results Hypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice. Conclusion Our findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.

scholarly journals Soluble advanced glycosylation receptor is a potential target for the treatment of neutrophilic asthma

2020 ◽  
Author(s):  
Xiaobo Zhang ◽  
Jun Xie ◽  
Hongmei Sun ◽  
Qing Wei ◽  
Ying Tao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Lavage Fluid ◽  
Pi3k Inhibitor ◽  
Adeno Associated Virus ◽  
Advanced Glycosylation ◽  
E Cadherin

Abstract Background Neutrophilic asthma (NA) was a subtype of asthma. Soluble advanced glycosylation receptor (sRAGE) was considered to be associated with the neutrophilic airway. However, the role of sRAGE in NA still limited. Methods A NA mouse model was established and the levels of sRAGE in the bronchoalveolar lavage fluid (BALF) were measured by ELISA. Hematoxylin-eosin (HE) and Masson trichrome staining were used to identifying airway remodeling. Adeno-associated virus 9 (AAV9) overexpressed sRAGE and inhibitors for HMGB1, RAGE, and PI3K were used to intervene NA mouse model via tail-vein injection and intraperitoneally injection. Expressions of airway remodeling, EMT, and signaling markers were detected using qRT-PCR or western blotting. The levels of IL-17 and IL-6 in BALF were measured by ELISA. HMGB1 was applied to induce EMT of human bronchial epithelial cells (16HBE), then E-cadherin and vimentin expressions were examined after sRAGE, RAGE inhibitor, and PI3K inhibitor administration. Results sRAGE levels were significantly reduced in BALF and the airway remodeling was observed in the NA mouse model. AAV9-sRAGE significantly inhibited the neutrophilic airway inflammation, airway remodeling, and the expression of IL-17, IL-6, TGF-β1, RAGE, PI3K, and EMT markers -E-cadherin and vimentin in vivo. HMGB1 inhibitor, RAGE inhibitor, and PI3K inhibitor upregulated E-cadherin level. Moreover, HMGB1 promoted the EMT process via RAGE/PI3K in 16HBE cells and sRAGE reversed HMGB1- induced EMT in vitro. Conclusion sRAGE levels decrease in the mouse model with NA. sRAGE treatment attenuates neutrophilic airway inflammation, airway remodeling, and EMT. This suggests sRAGE may yield benefits in the treatment of NA.

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