Mycoplasma pneumoniaeinfection increases airway collagen deposition in a murine model of allergic airway inflammation

Mycoplasma pneumoniae (Mp) has been linked to chronic asthma. Airway remodeling (e.g., airway collagen deposition or fibrosis) is one of the pathological features of chronic asthma. However, the effects of respiratory Mp infection on airway fibrosis in asthma remain unclear. In the present study, we hypothesized that respiratory Mp infection may increase the airway collagen deposition in a murine model of allergic airway inflammation in part through upregulation of transforming growth factor (TGF)-β1. Double (2 wk apart) inoculations of Mp or saline (control) were given to mice with or without previous allergen (ovalbumin) challenges. On days 14 and 42 after the last Mp or saline, lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analyses of collagen and TGF-β1 at protein and mRNA levels. In allergen-naïve mice, Mp did not alter airway wall collagen. In allergen-challenged mice, Mp infections did not change airway wall collagen deposition on day 14 but increased the airway collagen on day 42; this increase was accompanied by increased TGF-β1 protein in the airway wall and reduced TGF-β1 protein release from the lung tissue into BAL fluid. Our results suggest that Mp infections could modulate airway collagen deposition in a murine model of allergic airway inflammation with TGF-β1 involved in the collagen deposition process.

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

Natural Product Communications ◽

10.1177/1934578x1501000210 ◽

2015 ◽

Vol 10 (2) ◽

pp. 1934578X1501000 ◽

Cited By ~ 4

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.

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Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00362.2017 ◽

2019 ◽

Vol 316 (1) ◽

pp. L245-L254 ◽

Cited By ~ 6

Author(s):

Yuqing Mo ◽

Kan Zhang ◽

Yuchen Feng ◽

Lingling Yi ◽

Yuxia Liang ◽

...

Keyword(s):

Epithelial Cells ◽

Airway Inflammation ◽

Murine Model ◽

Allergic Airway Inflammation ◽

Bronchial Epithelial Cells ◽

Mrna Levels ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Airway Eosinophilia

Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in an animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR) and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN, and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.

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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02072-0 ◽

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.

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A Specific PAI-1 Inhibitor, PAI-039, Reduced Airway Inflammation And Collagen Deposition In An Ova-challenged Murine Model Of Chronic Asthma

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2010.12.261 ◽

2011 ◽

Vol 127 (2) ◽

pp. AB63-AB63

Author(s):

S. Lee ◽

M. Eren ◽

D.E. Vaughan ◽

S.H. Cho

Keyword(s):

Airway Inflammation ◽

Murine Model ◽

Chronic Asthma ◽

Collagen Deposition ◽

Pai 1

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Anisakis pegreffii Extract Induces Airway Inflammation with Airway Remodeling in a Murine Model System

BioMed Research International ◽

10.1155/2021/2522305 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jun Ho Choi ◽

Ju Yeong Kim ◽

Myung-hee Yi ◽

Myungjun Kim ◽

Tai-Soon Yong

Keyword(s):

T Cells ◽

Inflammatory Response ◽

Airway Inflammation ◽

Lung Tissue ◽

Respiratory System ◽

Murine Model ◽

Lung Inflammation ◽

Airway Remodeling ◽

Collagen Deposition ◽

Anisakis Pegreffii

Exposure of the respiratory system to the Anisakis pegreffii L3 crude extract (AE) induces airway inflammation; however, the mechanism underlying this inflammatory response remains unknown. AE contains allergens that promote allergic inflammation; exposure to AE may potentially lead to asthma. In this study, we aimed to establish a murine model to assess the effects of AE on characteristic features of chronic asthma, including airway hypersensitivity (AHR), airway inflammation, and airway remodeling. Mice were sensitized for five consecutive days each week for 4 weeks. AHR, lung inflammation, and airway remodeling were evaluated 24 h after the last exposure. Lung inflammation and airway remodeling were assessed from the bronchoalveolar lavage fluid (BALF). To confirm the immune response in the lungs, changes in gene expression in the lung tissue were assessed with reverse transcription-quantitative PCR. The levels of IgE, IgG1, and IgG2a in blood and cytokine levels in the BALF, splenocyte, and lung lymph node (LLN) culture supernatant were measured with ELISA. An increase in AHR was prominently observed in AE-exposed mice. Epithelial proliferation and infiltration of inflammatory cells were observed in the BALF and lung tissue sections. Collagen deposition was detected in lung tissues. AE exposure increased IL-4, IL-5, and IL-13 expression in the lung, as well as the levels of antibodies specific to AE. IL-4, IL-5, and IL-13 were upregulated only in LLN. These findings indicate that an increase in IL-4+ CD4+ T cells in the LLN and splenocyte resulted in increased Th2 response to AE exposure. Exposure of the respiratory system to AE resulted in an increased allergen-induced Th2 inflammatory response and AHR through accumulation of inflammatory and IL-4+ CD4+ T cells and collagen deposition. It was confirmed that A. pegreffii plays an essential role in causing asthma in mouse models and has the potential to cause similar effects in humans.

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