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 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 Statins attenuate antiviral IFN-β and ISG expression via inhibiting IRF3/JAK/STAT signaling in poly(I:C)-treated hyperlipidemic mice and macrophages

2020 ◽  
Author(s):  
Atsushi Koike ◽  
Kaito Tsujinaka ◽  
Ko Fujimori
Keyword(s):  
Bronchoalveolar Lavage ◽  
Molecular Mechanisms ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Janus Kinase ◽  
Poly I:C ◽  
Induced Expression ◽  
Antiviral Immune Response ◽  
Polycytidylic Acid ◽  
Stat Signaling

AbstractViral infection is a significant burden to healthcare worldwide. Statins, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, are widely used as cholesterol-lowering drugs. Recently, long term statin therapy was shown to reduce the antiviral immune response; however, the underlying molecular mechanisms are unclear. Here, we found that simvastatin decreased polyinosinic-polycytidylic acid [poly(I:C)]-induced expression of antiviral interferon (IFN)-β and IFN-stimulated genes (ISGs) in the bronchoalveolar lavage fluid and lungs of mice with high-fat diet-induced hyperlipidemia. As macrophages were the dominant cell type in the bronchoalveolar lavage fluid of poly(I:C)-treated mice, we examined the molecular mechanisms of statin-mediated inhibition of antiviral gene expression using murine J774.1/JA-4 macrophages. Simvastatin and pitavastatin decreased poly(I:C)-induced expression of IFN-β and ISGs. Moreover, they repressed poly(I:C)-induced phosphorylation of IFN regulatory factor (IRF) 3 and signal transducers and activators of transcription (STAT) 1, which is involved in Janus kinase (JAK)/STAT signaling. Mevalonate and geranylgeranylpyrophosphate (GGPP), but not cholesterol, counteracted the negative effect of statins on IFN-β and ISG expression and phosphorylation of IRF3 and STAT1. These results suggest that statins suppressed the expression of IFN-β and ISGs in poly(I:C)-treated hyperlipidemic mice and murine macrophages, and that these effects occured through the inhibition of IRF3-mediated JAK/STAT signaling in macrophages. Furthermore, GGPP recovered the statin-suppressed IRF3/JAK/STAT signaling pathway in poly(I:C)-treated macrophages.

scholarly journals MTOR-Mediated Autophagy Is Involved in the Protective Effect of Ketamine on Allergic Airway Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Hongyun Zou ◽  
Li-Xia Wang ◽  
Muzi Wang ◽  
Cheng Cheng ◽  
Shuai Li ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Protective Effect ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Mammalian Target Of Rapamycin ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Morphological Findings ◽  
Airway Diseases ◽  
Inflammatory Mechanism

Unresolved inflammation underpins the pathogenesis of allergic airway diseases, such as asthma. Ketamine, accepted as a promising therapy for resistant asthma, has been demonstrated to attenuate allergic airway inflammation. However, the anti-inflammatory mechanism by ketamine in this setting is largely unknown. We aimed to investigate whether autophagy was involved in the protective effect of ketamine on allergic airway inflammation. Female C57BL/6 mice were sensitized to ovalbumin (OVA) and treated with ketamine at 25, 50, or 100 mg/kg prior to OVA challenge. In this model, the pulmonary morphological findings and airway inflammation were significantly inhibited at 50 mg/kg but not at 25 or 100 mg/kg. Moreover, 50 mg/kg ketamine abrogated the increased concentrations of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) of allergic mice, as well as activated the expression of phosphorylated mammalian target of rapamycin (p-MTOR) and inhibited autophagy in allergic mice. To confirm whether the effect of 50 mg/kg ketamine on asthma was mediated by inhibiting autophagy, rapamycin was administered to mice sensitized to OVA and exposed to 50 mg/kg ketamine. All of the effect of 50 mg/kg ketamine was reversed by rapamycin treatment, including increased p-MTOR and decreased autophagy. Taken together, the present study demonstrates that 50 mg/kg ketamine inhibits allergic airway inflammation by suppressed autophagy, and this effect is mediated by the activation of MTOR in the lungs of allergic mice.

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 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.

Comparison of metabolites in exhaled breath and bronchoalveolar lavage fluid samples in a mouse model of asthma

2011 ◽  
Vol 111 (4) ◽  
pp. 1088-1095 ◽  
Author(s):  
Stephanie Neuhaus ◽  
Luzia Seifert ◽  
Wolfgang Vautz ◽  
Jürgen Nolte ◽  
Albrecht Bufe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Exhaled Breath ◽  
Ion Mobility Spectrometer ◽  
Eosinophilic Granulocytes

Background: A multi-capillary column ion mobility spectrometer (MCC/IMS) was developed to provide a method for the noninvasive diagnosis of lung diseases. The possibility of measuring the exhaled breath of mice was evaluated previously. The aim of the present study was to reveal whether mice affected by airway inflammation can be identified via MCC/IMS. Methods: Ten mice were sensitized and challenged with ovalbumin to induce allergic airway inflammation. The breath and volatile compounds of bronchoalveolar lavage fluid (BALF) were measured by MCC/IMS. Furthermore, histamine, nitric oxide, and arachidonic acid were determined as inflammatory markers in vitro. Results: Six volatile molecules were found in the BALF headspace at a significantly higher concentration in mice with airway inflammation compared with healthy animals. The concentration of substances correlated with the numbers of infiltrating eosinophilic granulocytes. However, substances showing a significantly different concentration in the BALF headspace were not found to be different in exhaled breath. Histamine and nitric oxide were identified by MCC/IMS in vitro but not in the BALF headspace or exhaled breath. Conclusion: Airway inflammation in mice is detectable by the analysis of the BALF headspace via MCC/IMS. Molecules detected in the BALF headspace of asthmatic mice at a higher concentration than in healthy animals may originate from oxidative stress induced by airway inflammation. As already described for humans, we found no correlation between the biomarker concentration in the BALF and the breath of mice. We suggest using the model described here to gain deeper insights into this discrepancy.

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 Adipose-Derived Stem Cells Ameliorate Allergic Airway Inflammation by Inducing Regulatory T Cells in a Mouse Model of Asthma

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kyu-Sup Cho ◽  
Mi-Kyung Park ◽  
Shin-Ae Kang ◽  
Hee-Young Park ◽  
Sung-Lyong Hong ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Regulatory T Cells ◽  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Immune Cell ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Th2 Cytokines

Although several studies have demonstrated that mesenchymal stem cells derived from adipose tissue (ASCs) can ameliorate allergic airway inflammation, the immunomodulatory mechanism of ASCs remains unclear. In this study, we investigated whether regulatory T cells (Tregs) induction is a potential mechanism in immunomodulatory effects of ASCs on allergic airway disease and how these induced Tregs orchestrate allergic inflammation. Intravenous administration of ASCs significantly reduced allergic symptoms and inhibited eosinophilic inflammation. Airway hyperresponsiveness, total immune cell and eosinophils in the bronchoalveolar lavage fluid, mucus production, and serum allergen-specific IgE and IgG1 were significantly reduced after ASCs administration. ASCs significantly inhibited Th2 cytokines (IL-4, IL-5, and IL-13) and enhanced Th1 cytokine (IFN-γ) and regulatory cytokines (IL-10 and TGF-β) in the bronchoalveolar lavage fluid and lung draining lymph nodes. Furthermore, levels of IDO, TGF-β, and PGE2were significantly increased after ASCs administration. Interestingly, this upregulation was accompanied by increased Treg populations. In conclusion, ASCs ameliorated allergic airway inflammation and improved lung function through the induction of Treg expansion. The induction of Treg by ASCs involves the secretion of soluble factors such as IDO, TGF-β, and PGE2and Treg might be involved in the downregulation of Th2 cytokines and upregulation of Th1 cytokines production.

scholarly journals Allergin-1 Immunoreceptor Suppresses House Dust Mite–Induced Allergic Airway Inflammation

2020 ◽  
Vol 204 (4) ◽  
pp. 753-762 ◽  
Author(s):  
Haruka Miki ◽  
Satoko Tahara-Hanaoka ◽  
Mariana Silva Almeida ◽  
Kaori Hitomi ◽  
Shohei Shibagaki ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
House Dust ◽  
House Dust Mite ◽  
Allergic Airway Inflammation ◽  
Dust Mite
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