Antiasthmatic Effects of Hesperidin, a Potential Th2 Cytokine Antagonist, in a Mouse Model of Allergic Asthma

Background and Objective. The features of asthma are airway inflammation, reversible airflow obstruction, and an increased sensitivity to bronchoconstricting agents, termed airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of hesperidin as well as the underlying mechanism involved, we studied the inhibitory effect and anti-inflammatory effect of hesperidin (HPN) on the production of Th2 cytokines, eotaxin, IL-17, -OVA-specific IgEin vivoasthma model mice.Methods. In this paper, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of HPN on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA-specific IgE production in a mouse model of asthma.Results. In BALB/c mice, we found that HPN-treated groups had suppressed eosinophil infiltration, allergic airway inflammation, and AHR, and these occurred by suppressing the production of IL-5, IL-17, and OVA-specific IgE.Conclusions. Our data suggest that the therapeutic mechanism by which HPN effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production, and eosinophil infiltration via inhibition of GATA-3 transcription factor.

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Antiasthmatic Effects of Herbal Complex MA and Its Fermented Product MA128

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/769508 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Dong-Seon Kim ◽

Seung-Hyung Kim ◽

Bok-Kyu Kim ◽

Min Cheol Yang ◽

Jin Yeul Ma

Keyword(s):

Lactobacillus Acidophilus ◽

Airway Hyperresponsiveness ◽

Cytokine Production ◽

Immune Cell ◽

Allergic Airway Inflammation ◽

Lavage Fluid ◽

Specific Ige ◽

Eosinophil Infiltration ◽

Th2 Cytokine ◽

Fermented Product

This study was conducted to determine if oral administration of the novel herbal medicine, MA, and itsLactobacillus acidophilusfermented product, MA128, have therapeutic properties for the treatment of asthma. Asthma was induced in BALB/c mice by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges. MA and MA128 were orally administered 6 times a week for 4 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was assessed and samples of bronchoalveolar lavage fluid, lung cells, and serum were collected for further analysis. We investigated the effect of MA and MA128 on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, OVA-specific IgE production, and Th1/Th2 cytokine production in this mouse model of asthma. In BALB/c mice, we found that MA and MA128 treatment suppressed eosinophil infiltration into airways and blood, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13, IL-17, Eotaxin, and OVA-specific IgE, by upregulating the production of OVA-specific Th1 cytokine (IFN-γ), and by downregulating OVA-specific Th2 cytokine (IL-4) in the culture supernatant of spleen cells. The effectiveness of MA was increased by fermentation withLactobacillus acidophilus.

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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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Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2 Cytokines in Mice

Mediators of Inflammation ◽

10.1155/2017/7506808 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Yoon-Young Sung ◽

Seung-Hyung Kim ◽

Dong-Seon Kim ◽

Ji-eun Lee ◽

Ho Kyoung Kim

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Cytokine Production ◽

Foxp3 Expression ◽

Eosinophilic Infiltration ◽

Th2 Cytokines ◽

Th2 Cytokine ◽

Illicium Verum

Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans-anethole (AET), on airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3) expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness (p<0.01), pulmonary eosinophilic infiltration (p<0.05), mucus hypersecretion (p<0.01), and IL-4, IL-5, IL-13, and CCR3 production (p<0.05), as well as IgE levels (p<0.01). IVE and AET increased Foxp3 expression in lungs (p<0.05). IVE and AET reduced IL-4 and increased IFN-γ production in the supernatant of splenocyte cultures (p<0.05). Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p<0.01). These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3+ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.

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Pinellia ternata,Citrus reticulata, and Their Combinational Prescription Inhibit Eosinophil Infiltration and Airway Hyperresponsiveness by Suppressing CCR3+ and Th2 Cytokines Production in the Ovalbumin-Induced Asthma Model

Mediators of Inflammation ◽

10.1155/2009/413270 ◽

2009 ◽

Vol 2009 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

In-Soo Ok ◽

Seung-Hyung Kim ◽

Bok-Kyu Kim ◽

Jang-Cheon Lee ◽

Young-Cheol Lee

Keyword(s):

Murine Model ◽

Airway Hyperresponsiveness ◽

Immunoglobulin E ◽

Allergic Inflammation ◽

Eosinophil Infiltration ◽

Citrus Reticulata ◽

Th2 Cytokines ◽

Pinellia Ternata ◽

Th2 Cytokine ◽

Histamine Production

Background and Objective. This study was aimed to analyse the curative effects ofPinellia ternata,Citrus reticulata, and their combination on airway hyperresponsiveness (AHR) to inhaled methacholine, pulmonary eosinophilic infiltration, Th2 cytokine production, and IgE and histamine production in a murine model of asthma.Methods. For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges for 12 weeks. We examined the development of pulmonary eosinophilic accumulation, control of Th2 cytokine, immunoglobulin E (IgE), and histamine productions in a murine model of asthma.Results. Our data suggest that the therapeutic mechanism by whichPinellia ternata,Citrus reticulata, and their combinational prescription effectively treats asthma is based on reductions of eosinophil infiltration, eotaxin receptor (CCR3), histamine, OVA-specific IgE productions in serum, and Th2 cytokines (IL-5, IL-13) by marked reductions of IL-5 and IL-13 mRNA expression in lung tissue.Conclusions. These findings provide evidence thatPinellia ternata,Citrus reticulata, and their combination play a regulatory role in allergic inflammation and offer therapeutic approaches as novel CCR3 antagonists for treatment asthma. However, it is not clear whether pharmacological activities of prescription composed of two herbs are potentiated due to synergistic effect or additive effect.

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Alcohol reduces airway hyperresponsiveness (AHR) and allergic airway inflammation in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00077.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. L308-L315 ◽

Cited By ~ 17

Author(s):

Peter J. Oldenburg ◽

Jill A. Poole ◽

Joseph H. Sisson

Keyword(s):

Mouse Model ◽

Airway Inflammation ◽

Allergic Asthma ◽

Airway Hyperresponsiveness ◽

Immunoglobulin E ◽

Allergic Airway Inflammation ◽

Alcohol Exposure ◽

Lung Pathology ◽

Cell Counts

There is very limited knowledge about the effects of alcohol on airway hyperresponsiveness and inflammation in asthma. Historical accounts of alcohol administration to patients with breathing problems suggest that alcohol may have bronchodilating properties. We hypothesized that alcohol exposure will alter airway hyperresponsiveness (AHR) and pulmonary inflammation in a mouse model of allergic asthma. To test this hypothesis, BALB/c mice were fed either 18% alcohol or water and then sensitized and challenged with ovalbumin (OVA). AHR was assessed by means of ventilation or barometric plethysmography and reported as either total lung resistance or enhanced pause, respectively. Airway inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluid (BALF), cytokine levels in BALF, lung histology, and serum immunoglobulin E (IgE) levels. Alcohol feeding significantly blocked methacholine-induced increases in AHR compared with water-fed controls. Alcohol feeding significantly reduced total cell numbers (64%) as well as the number of eosinophils (84%) recruited to the lungs of these mice. Modest changes in lung pathology were also observed. Alcohol exposure led to a reduction of IgE in the serum of the EtOH OVA mice. These data demonstrate that alcohol exposure blunts AHR and dampens allergic airway inflammation indices in allergic mice and suggest that there may be an important role for alcohol in the modulation of asthma. These data provide an in vivo basis for previous clinical observations in humans substantiating the bronchodilator properties of alcohol and for the first time demonstrates an alcohol-induced reduction of allergic inflammatory cells in a mouse model of allergic asthma.

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Attenuation of allergen-induced airway hyperresponsiveness is mediated by airway regulatory T cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00521.2007 ◽

2009 ◽

Vol 296 (3) ◽

pp. L307-L319 ◽

Cited By ~ 38

Author(s):

Jennifer T. Burchell ◽

Matthew E. Wikstrom ◽

Philip A. Stumbles ◽

Peter D. Sly ◽

Debra J. Turner

Keyword(s):

Airway Hyperresponsiveness ◽

Transforming Growth Factor ◽

Airway Remodeling ◽

Allergic Diseases ◽

Transforming Growth Factor Β ◽

Specific Ige ◽

Treg Cells ◽

Th2 Cytokines ◽

Cell Counts

Understanding the mechanisms involved in respiratory tolerance to inhaled allergens could potentially result in improved therapies for asthma and allergic diseases. Airway hyperresponsiveness (AHR) is a major feature of allergic asthma, thus the aim of the current study was to investigate mechanisms underlying suppression of allergen-induced AHR during chronic allergen exposure. Adult BALB/c mice were systemically sensitized with ovalbumin (OVA) in adjuvant and then challenged with a single 3 or 6 wk of OVA aerosols. Airway and parenchymal responses to inhaled methacholine (MCh), inflammatory cell counts, cytokines, OVA-specific IgE and IgG1, parenchymal histology, and numbers of airway CD4+69+ activated and CD4+25+FoxP3+ regulatory T (Treg) cells were assessed 24 h after the final aerosol. Single OVA challenge resulted in AHR, eosinophilia, increased serum OVA-specific IgE, and T helper 2 (Th2) cytokines in bronchoalveolar lavage (BAL) but no difference in numbers of Treg compared with control mice. Three weeks of OVA challenges resulted in suppression of AHR and greater numbers of airway Treg cells and increased transforming growth factor-β1 (TGFβ1) compared with control mice despite the presence of increased eosinophilia, OVA-specific IgE and IgG1, and airway remodeling. Six weeks of OVA challenges restored AHR, whereas airway Treg numbers, TGFβ1, BAL eosinophilia, and Th2 cytokines returned to control levels. Partial in vivo depletion or adoptive transfer of Treg cells restored or inhibited AHR, respectively, but did not affect TGFβ1 or Th2 cytokine production. In conclusion, AHR suppression is mediated by airway Treg cells and potentially via a paracrine induction of TGFβ1 in the airways.

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Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-019-0396-4 ◽

2019 ◽

Vol 15 (1) ◽

Author(s):

Yahao Ren ◽

Takamichi Ichinose ◽

Miao He ◽

Seiichi Youshida ◽

Masataka Nishikawa ◽

...

Keyword(s):

Airway Inflammation ◽

Immune Cell ◽

Adaptor Protein ◽

Lavage Fluid ◽

Specific Ige ◽

Pathological Changes ◽

Th2 Response ◽

Lung Eosinophilia ◽

High Concentrations

Abstract Background Lipopolysaccharide (LPS) often presents in high concentrations in particulate matter (PM), few studies have reported the enhancing effects of both LPS and PM on airway inflammation in mice and the role of toll-like receptors (TLRs) in this process. Asian sand dust (ASD) is observed most frequently during the spring. This study aimed to clarify the role of TLRs in murine lung eosinophilia exacerbated by ASD and LPS. Methods The effects of LPS and ASD co-treatment on ovalbumin (OVA)-induced lung eosinophilia were investigated using wild-type (WT), TLR2−/−, TLR4−/−, and adaptor protein myeloid differentiation factor 88 (MyD88)−/− BALB/c mice. ASD was heated (H-ASD) to remove the toxic organic substances. WT, TLR2−/−, TLR4−/− and MyD88−/− BALB/c mice were intratracheally instilled with four different combinations of LPS, H-ASD and OVA treatment. Subsequently, the pathological changes in lungs, immune cell profiles in bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines levels in BALF and OVA-specific immunoglobulin (Ig) in serum were analyzed. Results In WT mice, H-ASD + LPS exacerbated OVA-induced lung eosinophilia. This combination of treatments increased the proportion of eosinophils and the levels of IL-5, IL-13, eotaxin in BALF, as well as the production of OVA-specific IgE and IgG1 in serum compared to OVA treatment alone. Although these effects were stronger in TLR2−/− mice than in TLR4−/− mice, the expression levels of IL-5, IL-13, eotaxin were somewhat increased in TLR4−/− mice treated with OVA + H-ASD + LPS. In MyD88−/− mice, this pro-inflammatory mediator-induced airway inflammation was considerably weak and the pathological changes in lungs were negligible. Conclusions These results suggest that LPS and H-ASD activate OVA-induced Th2 response in mice, and exacerbate lung eosinophilia via TLR4/MyD88, TLR4/TRIF and other TLR4-independent pathways.

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