P2Y12 antagonist attenuates eosinophilic inflammation and airway hyperresponsiveness in a mouse model of asthma

Abstract Background: It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet-eosinophil aggregation (PEA) in asthma.Methods: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28-30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 minutes before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated.Results: Tirofiban treatment decreased AHR and eosinophilic inflammation in BAL fluid. This treatment also reduced the levels of IL-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice.Conclusion: The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

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Cigarette Smoke-induced Airway Hyperresponsiveness Is Not Dependent on Elevated Immunoglobulin and Eosinophilic Inflammation in a Mouse Model of Allergic Airway Disease

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.2106029 ◽

2002 ◽

Vol 165 (10) ◽

pp. 1410-1418 ◽

Cited By ~ 47

Author(s):

Edward G. Barrett ◽

Julie A. Wilder ◽

Thomas H. March ◽

Teresa Espindola ◽

David E. Bice

Keyword(s):

Mouse Model ◽

Cigarette Smoke ◽

Airway Hyperresponsiveness ◽

Airway Disease ◽

Allergic Airway Disease ◽

Eosinophilic Inflammation

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The blocking effect of the glycoprotein IIb/IIIa receptor in the mouse model of asthma

Clinical and Molecular Allergy ◽

10.1186/s12948-021-00149-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Seo-Hee Kim ◽

Hoang Kim Tu Trinh ◽

Hae-Sim Park ◽

Yoo Seob Shin

Keyword(s):

Mouse Model ◽

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Inflammatory Cell ◽

Critical Role ◽

Allergic Inflammation ◽

Positive Control ◽

Blocking Effect ◽

Histological Evaluation ◽

Eosinophilic Inflammation

Abstract Background It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet–eosinophil aggregation (PEA) in asthma. Methods BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28–30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 min before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated. Results Tirofiban treatment decreased AHR and eosinophilic inflammation in Bronchoalveolar Lavage (BAL) fluid. This treatment also reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice. Conclusions The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.

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Faculty Opinions recommendation of A dissociated glucocorticoid receptor modulator reduces airway hyperresponsiveness and inflammation in a mouse model of asthma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.716398061.791803121 ◽

2012 ◽

Author(s):

Yassine Amrani

Keyword(s):

Mouse Model ◽

Glucocorticoid Receptor ◽

Airway Hyperresponsiveness ◽

Receptor Modulator

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IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model

Current Eye Research ◽

10.1080/02713683.2021.1874022 ◽

2021 ◽

pp. 1-10

Author(s):

Yukiko Shiraki ◽

Jun Shoji ◽

Noriko Inada ◽

Akiko Tomioka ◽

Satoru Yamagami

Keyword(s):

Mouse Model ◽

House Dust ◽

House Dust Mite ◽

Eosinophilic Inflammation ◽

Atopic Keratoconjunctivitis ◽

Dust Mite ◽

Dose Dependent

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Effects of Thymus vulgaris L., Cinnamomum verum J.Presl and Cymbopogon nardus (L.) Rendle Essential Oils in the Endotoxin-induced Acute Airway Inflammation Mouse Model

Molecules ◽

10.3390/molecules25153553 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3553

Author(s):

Eszter Csikós ◽

Kata Csekő ◽

Amir Reza Ashraf ◽

Ágnes Kemény ◽

László Kereskai ◽

...

Keyword(s):

Mouse Model ◽

Essential Oils ◽

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Whole Body ◽

Gas Chromatography Mass Spectrometry ◽

Thymus Vulgaris ◽

Inflammatory Conditions ◽

Inflammatory Parameters

Thyme (TO), cinnamon (CO), and Ceylon type lemongrass (LO) essential oils (EOs) are commonly used for inhalation. However, their effects and mechanisms on inflammatory processes are not well-documented, and the number of in vivo data that would be important to determine their potential benefits or risks is low. Therefore, we analyzed the chemical composition and investigated the activity of TO, CO, and LO on airway functions and inflammatory parameters in an acute pneumonitis mouse model. The components of commercially available EOs were measured by gas chromatography–mass spectrometry. Airway inflammation was induced by intratracheal endotoxin administration in mice. EOs were inhaled during the experiments. Airway function and hyperresponsiveness were determined by unrestrained whole-body plethysmography on conscious animals. Myeloperoxidase (MPO) activity was measured by spectrophotometry from lung tissue homogenates, from which semiquantitative histopathological scores were assessed. The main components of TO, CO, and LO were thymol, cinnamaldehyde, and citronellal, respectively. We provide here the first evidence that TO and CO reduce inflammatory airway hyperresponsiveness and certain cellular inflammatory parameters, so they can potentially be considered as adjuvant treatments in respiratory inflammatory conditions. In contrast, Ceylon type LO inhalation might have an irritant effect (e.g., increased airway hyperresponsiveness and MPO activity) on the inflamed airways, and therefore should be avoided.

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High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma

Scientific Reports ◽

10.1038/s41598-020-77947-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Laura Hesse ◽

N. van Ieperen ◽

Arjen H. Petersen ◽

J. N. G. Oude Elberink ◽

Antoon J. M. van Oosterhout ◽

...

Keyword(s):

Mouse Model ◽

Grass Pollen ◽

Airway Hyperresponsiveness ◽

Allergic Inflammation ◽

Optimal Dose ◽

Lavage Fluid ◽

Subcutaneous Immunotherapy ◽

High Dose ◽

Allergen Specific Immunotherapy ◽

Neutralizing Capacity

AbstractAllergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens.

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