scholarly journals Sevoflurane Inhibits the Th2 Response and NLRP3 Expression in Murine Allergic Airway Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Lixia Wang ◽  
Binshan Zha ◽  
Qiying Shen ◽  
Hongyun Zou ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Th2 Response ◽  
Cell Hyperplasia ◽  
Mucus Production ◽  
Caspase 1 ◽  
Nlrp3 Expression

Background. Our colleagues have demonstrated an impressive therapeutic role of sevoflurane in a murine allergic airway inflammation model, but the mechanisms underlying this effect remain undefined. In this study, we tried to investigate the effect of sevoflurane on the resolution of allergic airway inflammation and to assess whether NLRP3 or the NLRP3 inflammasome is involved in this process. Methods. Female (C57BL/6) mice were sensitized and challenged with ovalbumin (OVA). Then, some of the mice received MCC950 (10 mg/kg; i.p.) or 3% sevoflurane. Total and differential inflammatory cell numbers, proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), the peribronchial inflammation density, and mucus production were evaluated. In addition, we analysed the protein levels of NLRP3, the apoptosis-associated speck-like protein containing the caspase activation and recruitment domain (ASC), pro-caspase-1, and caspase-1 in the lung tissue. Results. We found that OVA-induced inflammatory cell recruitment to peribronchial regions, goblet cell hyperplasia, the serum levels of IgE, inflammatory cells, and the Th2 cytokine secretion in BALF was potently suppressed by sevoflurane with an efficacy comparable with that suppressed by MCC950 treatment. Furthermore, sevoflurane, similar to MCC950, clearly inhibited the OVA-induced activity of NLRP3 in the lungs. In addition, we found that OVA challenge failed to increase the expression of ASC, pro-caspase-1, and caspase-1 in the lungs and the levels of IL-18 and IL-1β in BALF. Conclusion. Taken together, our data showed that sevoflurane ameliorated allergic airway inflammation by inhibiting Th2 responses and NLRP3 expression. The NLRP3 independent of inflammasomes participated in the pathogenesis of allergic asthma in this model.

scholarly journals The Fermented Soy Product ImmuBalanceTM Suppresses Airway Inflammation in a Murine Model of Asthma

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3380
Author(s):  
Hideaki Kadotani ◽  
Kazuhisa Asai ◽  
Atsushi Miyamoto ◽  
Kohei Iwasaki ◽  
Takahiro Kawai ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Murine Model ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Cell Infiltration ◽  
Mucus Production ◽  
Cell Counts

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.

scholarly journals Diabetes Downregulates Allergen-Induced Airway Inflammation in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Vinicius F. Carvalho ◽  
Emiliano O. Barreto ◽  
Ana Carolina S. Arantes ◽  
Magda F. Serra ◽  
Tatiana Paula T. Ferreira ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Allergic Airway Inflammation ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Airway Hyperreactivity ◽  
Eosinophil Infiltration ◽  
Mucus Production ◽  
Diabetes Induction

Previous studies described that allergic diseases, including asthma, occur less often than expected in patients with type 1 diabetes. Here, we investigated the influence of diabetes on allergic airway inflammation in a model of experimental asthma in mice. Diabetes was induced by intravenous injection of alloxan into 12 h-fasted A/J mice, followed by subcutaneous sensitization with ovalbumin (OVA) and aluminum hydroxide (Al(OH)3), on days 5 and 19 after diabetes induction. Animals were intranasally challenged with OVA (25 μg), from day 24 to day 26. Alloxan-induced diabetes significantly attenuated airway inflammation as attested by the lower number of total leukocytes in the bronchoalveolar lavage fluid, mainly neutrophils and eosinophils. Suppression of eosinophil infiltration in the peribronchiolar space and generation of eosinophilotactic mediators, such as CCL-11/eotaxin, CCL-3/MIP-1α, and IL-5, were noted in the lungs of diabetic sensitized mice. In parallel, reduction of airway hyperreactivity (AHR) to methacholine, mucus production, and serum IgE levels was also noted under diabetic conditions. Our findings show that alloxan diabetes caused attenuation of lung allergic inflammatory response in A/J mice, by a mechanism possibly associated with downregulation of IgE antibody production.

scholarly journals Reduction of Airway Hyperresponsiveness by KWLL inDermatophagoides-pteronyssinus-Challenged Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9
Author(s):  
Chih-Che Lin ◽  
Shulhn-Der Wang ◽  
Li-Jen Lin ◽  
Hong-Jye Hong ◽  
Chin-Jen Wu ◽  
...  
Keyword(s):  
Airway Hyperresponsiveness ◽  
Bronchoalveolar Lavage Fluid ◽  
Expression Profiles ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Eosinophil Infiltration ◽  
Cell Hyperplasia ◽  
Ancient Civilizations ◽  
Airway Hypersensitivity

Urine therapy has been commonly practiced in ancient civilizations including those of India, China, and Greece. The traditional Chinese medicine KWLL, the precipitation of human urine, has been used in China to alleviate the symptoms of asthma for thousands of years. However, the mechanism of action by which KWLL exerts its immunotherapy is unclear. This study attempted to elucidate the pharmacology of KWLL in mice that had been challenged recurrently byDermatophagoides pteronyssinus(Der p). BALB/c mice were orally administered KWLL (1 g/kg) before an intratracheal (i.t.) challenge of Der p. Allergic airway inflammation and remodeling were provoked by repetitive Der p (50 μg/mice) challenges six times at 1 wk intervals. Airway hypersensitivity, histological lung characteristics, and the expression profiles of cytokines and various genes were assessed. KWLL reduced Der p-induced airway hyperresponsiveness and inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in bronchoalveolar lavage fluid (BALF). It also inhibited neutrophil recruitment by downregulating IL-17A in BALF. KWLL effectively diminished inflammatory cells, goblet cell hyperplasia, and mRNA expression of IL-6 and IL-17A in the lung. The reduction by KWLL of airway inflammatory and hyperresponsiveness in allergic asthmatic mice was mediated via immunomodulation of IL-5, IL-6, and IL-17A.

scholarly journals Alnus hirsuta (Spach) Rupr. Attenuates Airway Inflammation and Mucus Overproduction in a Murine Model of Ovalbumin-Challenged Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
Ba-Wool Lee ◽  
Ji-Hye Ha ◽  
Yeongseon Ji ◽  
Seong-Hun Jeong ◽  
Ju-Hong Kim ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Asthma ◽  
Immunoglobulin E ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Th2 Cytokines ◽  
Protective Effects ◽  
Mucus Production ◽  
Tnf Α ◽  
Alnus Hirsuta

Alnus hirsuta (Spach) Rupr. (AH), a member of the Betulaceae family, is widely used in Eastern Asia of as a source of medicinal compounds for the treatment of hemorrhage, diarrhea, and alcoholism. In this study, we investigated the protective effects of a methanolic extract of AH branches against airway inflammation and mucus production in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in an ovalbumin (OVA)-challenged allergic asthma mouse model. Female BALB/c mice were injected with OVA (40 μg) and aluminum hydroxide (2 mg) on days 0 and 14 to induce allergic airway inflammation. The mice were then challenged with 1% OVA from days 21–23. Mice were treated with AH (50 and 100 mg/kg/day; 2% DMSO) or dexamethasone (positive control; 3 mg/kg/day) from days 18–23. AH treatment effectively attenuated airway resistance/hyperresponsiveness and reduced levels of T helper type 2 (Th2) cytokines, eotaxins, and number of inflammatory cells in bronchoalveolar lavage fluid, and immunoglobulin E in serums of OVA-challenged mice. In histological analysis, AH treatment significantly inhibited airway inflammation and mucus production in OVA-challenged mice. AH treatment downregulated the phosphorylation of I kappa B-alpha, p65 nuclear factor-kappa B (p65NF-κB), and mitogen-activated protein kinases with suppression of mucin 5AC (MUC5AC) in lung tissue. Moreover, AH treatment decreased the levels of pro-inflammatory cytokines and Th2 cytokines, as well as MUC5AC expression, and inhibited the phosphorylation of p65NF-κB in TNF-α-stimulated NCI-H292 cells. These results indicate that AH might represent a useful therapeutic agent for the treatment of allergic asthma.

scholarly journals The non-antibiotic macrolide EM900 attenuates HDM and poly(I:C)-induced airway inflammation with inhibition of macrophages in a mouse model

2019 ◽  
Vol 69 (1) ◽  
pp. 139-151 ◽  
Author(s):  
Hironori Sadamatsu ◽  
Koichiro Takahashi ◽  
Hiroki Tashiro ◽  
Go Kato ◽  
Yoshihiko Noguchi ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Poly I:C ◽  
Inhibitory Effects ◽  
Polycytidylic Acid ◽  
Bacterial Drug Resistance ◽  
Dust Mite

Abstract Objective Macrolides have been reported to reduce the exacerbation of severe asthma. The aim of this study was to clarify the effects and mechanisms of EM900, a non-antibiotic macrolide, on allergic airway inflammation. Methods Mice were sensitized and challenged by house dust mite (HDM), then exposed to polyinosinic-polycytidylic acid (poly(I:C)) as a model of asthma complicated with viral infection. Mice were administered with EM900. Airway inflammation was assessed from inflammatory cells in bronchoalveolar lavage fluid (BALF) and cytokines in lung tissues. Lung interstitial macrophages were counted by flow cytometry. Cytokine production, phosphorylation of NF-κB, and p38 in macrophages were examined by ELISA and western blotting. Results Counts of cells in BALF and concentrations of IL-13, IL-5, RANTES, IL-17A, and MIP-2 were significantly decreased by EM900 compared to those without EM900. Percentages of lung interstitial macrophages were significantly decreased with EM900. Concentrations of IL-6, RANTES, and MIP-2 induced by HDM and poly(I:C) were significantly suppressed by EM900 through the suppression of NF-κB and p38 phosphorylation in macrophages. Conclusions HDM and poly(I:C)-induced airway inflammation is attenuated by EM900 with the inhibition of lung interstitial macrophages. Clinical use of EM900 is expected, because EM900 has inhibitory effects against airway inflammation without inducing bacterial drug resistance.

scholarly journals Estrogen ameliorates allergic airway inflammation by regulating activation of NLRP3 in mice

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Cheng Cheng ◽  
Huimei Wu ◽  
Muzi Wang ◽  
Lixia Wang ◽  
Hongyun Zou ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Cytokine ◽  
Allergic Airway Inflammation ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Inflammasome Activation ◽  
Mucus Production ◽  
Caspase 1 ◽  
Pyrin Domain

Abstract Background: Estrogen has been suggested to play a protective role against airway inflammations, such as asthma. In these processes, the inflammasome nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) partly accounts for the activation of pro-inflammatory factors. The aim of the present study was to investigate whether NLRP3 was involved in the protective effect of estrogen against allergic airway inflammation. Methods: An ovariectomy was performed on female C57BL/6 mice; some were sham-operated (sham). We then sensitized and challenged them with ovalbumin (OVA) to establish an airway inflammation model. Meanwhile, some mice were treated with 17β-estradiol (E2) for 28 days. Results: The expression of NLRP3 inflammasome and its downstream products, caspase-1 and the pro-inflammatory cytokine interleukin (IL)-1β (IL-1β), increased concomitantly with OVA-challenged airway inflammation and decreased with the expression of estrogen receptor β (ERβ). In addition, treating ovariectomized (OVX) mice with E2 dramatically ameliorated airway inflammation via such mechanisms as leukocyte recruitment, mucus production, and secretion of pro-inflammatory cytokines other than IL-18 in bronchoalveolar lavage (BAL) fluid (BALF). Furthermore, E2 suppressed both the mRNA expression and protein expression of NLRP3, caspase-1, and IL-1β. In summary, our study showed that NLRP3 inflammasome activation and pro-inflammatory cytokine production markedly increased in OVA-induced airway inflammation, and E2 effectively abrogated such inflammation by regulating the activation of NLRP3.

scholarly journals Airway Inflammation and the Pathogenesis of Asthma

1994 ◽  
Vol 1 (3) ◽  
pp. 189-195 ◽  
Author(s):  
Paul M O'Byrne
Keyword(s):  
Mast Cells ◽  
Airway Inflammation ◽  
Structural Changes ◽  
Treatment Strategies ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Inflammatory Cell Infiltrate ◽  
Cell Hyperplasia ◽  
Characteristic Type ◽  
Macrophage Colony

Airway inflammation has been recognized for more than l00 years to be present in the airways of patients with severe asthma. Much more recently, airway intlammation has been identified to be central to the pathogenesis of all asthma. The inflammation is of a characteristic type, with the presence of activated eosinophils, mast cells and lymphocytes in bronchoalveolar lavage fluid and airway biopsies from patients with even mild asthma. Stimuli that are known to worsen asthma, such as inhaled allergens, also increase the numbers of mast cells and cosinophils in asthmatic airways. In addition, treatment with inhaled corticoteroids - the most effective treatment for asthma - improves symptoms and reduces the numbers of eosinophil s, mast cells and lymphocytes in the airways. The precise functions of the cells in promoting inflammation and causing asthma symptoms has not yet been fully elucidated. However, it is very likely that eicosanoids, such as the cysteinyl leukotrienes, are produced by eosinophils and mast cells and are a major cause of bronchoconstriction in asthma. Also, these inflammatory cells can produce proinflammatory cytokines, such as granulocytc-macrophage colony-stimulating factor. interleukin (IL) 3 and IL-5, which may promote continuing inflammation in the airways. Lastly, the persisting inflammatory cell infiltrate and products re leased from these cells arc very likely the cause or the airway structural changes characteristic of asthma, such as epithelial damage, goblet cell hyperplasia. smooth muscle thickening and deposition of collagen below the basement membrane. These changes have been suggested tn he the cause of airway hyperresponsiveness in asthma. An improved understanding of the precise mechanisms by which airway inflammation is initiated, propagates and causes airway damage will hopefully allow more precise treatment strategies to he developed for asthma than currently exist.

Blockade of the NLRP3/Caspase-1 Axis Ameliorates Airway Neutrophilic Inflammation in a Toluene Diisocyanate-Induced Murine Asthma Model

2019 ◽  
Vol 170 (2) ◽  
pp. 462-475 ◽  
Author(s):  
Shuyu Chen ◽  
Lihong Yao ◽  
Peikai Huang ◽  
Qiaoling He ◽  
Hongbing Guan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Remodeling ◽  
Lavage Fluid ◽  
Vital Role ◽  
Toluene Diisocyanate ◽  
Receptor Protein ◽  
Th2 Response ◽  
Caspase 1 ◽  
Asthma Model

Abstract Multiple studies have addressed the vital role of Nod-like receptor protein 3(NLRP3)/caspase-1/IL-1β signaling in asthma. Yet, the role of NLRP3/caspase-1 in toluene diisocyanate (TDI)-induced asthma is still obscure. The aim of this study is to investigate the role of the NLRP3/caspase-1 axis in TDI-induced asthma. Using an established murine model of TDI-induced asthma as described previously, we gave the asthmatic mice a highly selective NLRP3 inhibitor, MCC950, as well as the specific caspase-1 inhibitors VX-765 and Ac-YVAD-CHO for therapeutic purposes. Airway resistance was measured and bronchoalveolar lavage fluid was analyzed. Lungs were examined by histology, immunohistochemistry, Western blotting, and flow cytometry. TDI exposure elevated the expression of NLRP3 and caspase-1 that was coupled with increased airway hyperresponsiveness (AHR), neutrophil-dominated cell infiltration, pronounced goblet cell metaplasia, extensive collagen deposition, and increased TH2/TH17 responses. Both VX-765 and Ac-YVAD-CHO effectively inhibited the activation of caspase-1 in TDI-asthmatic mice that was accompanied by dramatic attenuation of AHR, airway inflammation, and airway remodeling, in addition to a decreased TH2 response and lower levels of IL-18 and IL-1β. MCC950 blocked the activation of NLRP3 and downregulated protein expression of caspase-1, IL-1β, and IL-18 in TDI-exposed mice. Furthermore, MCC950 remarkably alleviated AHR, airway inflammation, airway remodeling, and significantly suppressed TH2/TH17 responses. These findings suggested that blockade of the NLRP3/caspase-1 axis effectively prevents the progression of TDI-induced asthma and could be used as therapeutic targets for asthmatics.

scholarly journals Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation

Thorax ◽  
2020 ◽  
Vol 75 (7) ◽  
pp. 600-605
Author(s):  
Jennifer M Felton ◽  
David A Dorward ◽  
Jennifer A Cartwright ◽  
Philippe MD Potey ◽  
Calum T Robb ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Kinase Inhibitor ◽  
Allergic Airway Inflammation ◽  
Allergic Diseases ◽  
Airway Disease ◽  
Lavage Fluid ◽  
Allergic Airway Disease ◽  
Cyclin Dependent Kinase ◽  
Mucus Production ◽  
Effector Cells

Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production. Eosinophil apoptosis was suppressed by Mcl-1 overexpression, with this resistance to apoptosis attenuated by cyclin-dependent kinase inhibition which also rescued Mcl-1-exacerbated allergic airway inflammation. We propose that targeting Mcl-1 may be beneficial in treatment of allergic airway disease.

scholarly journals Antiasthmatic Effects of Sanglong Pingchuan Decoction through Inducing a Balanced Th1/Th2 Immune Response

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Binnian Zhu ◽  
Jun Dong ◽  
Xiangyun Gao ◽  
Yanfei He ◽  
Hongxiang Sun
Keyword(s):  
Mrna Expression ◽  
Airway Inflammation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Th2 Cytokines ◽  
Th2 Response ◽  
Total Ige ◽  
Expression Levels ◽  
Th2 Immune Response ◽  
Mrna Expression Levels

Objective. To investigate the antiasthmatic effects of Sanglong pingchuan decoction (SLPCD) and to explore its mechanisms of action. Methods. The serum, bronchoalveolar lavage fluid (BALF), and lung tissues from OVA-induced allergic asthma mice were collected 24 h after the last administration. Lung pathological changes were observed by H&E staining. The inflammatory cells in BALF were counted by flow cytometry. The levels of total IgE in serum and cytokines in BALF were determined by ELISA. The expression levels of cytokine mRNA in lung were assayed by qRT-PCR. Results. SLPCD significantly inhibited airway inflammation, reduced inflammatory cells in BALF, reduced the levels of total IgE in serum and Th2 cytokines (IL-10 and IL-13) in BALF, and downregulated the mRNA expression levels of Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) in lung of asthmatic mice. However, SLPCD remarkably elevated the level of Th1 cytokine IFN-γ in BALF and upregulated the mRNA expression levels of Th1 cytokines (IL-2 and IFN-γ) in lung of asthmatic mice. Conclusion. SLPCD could attenuate airway inflammation and alleviate the pathogenesis in asthma mice through inducing a balanced Th1/Th2 response and could act as an effective drug for treatment of asthma.

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