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Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.

ABSTRACT: Neutrophil-predominant asthma is less responsive to steroids and associated with poorer disease control. The effects of Antiasthma Simplified Herbal Medicine Intervention (ASHMI), a traditional Chinese medicine formula reported to be efficacious in asthmatic patients and murine asthma models, on neutrophil predominant asthma are unknown.To determine the effects of standard ASHMI and refined formula ASHMI (ASHMI(II)) in a neutrophil-predominant murine model of ragweed (RW) asthma and explore underlying mechanisms.BALB/c mice were systemically sensitized, intranasally challenged with RW extract, and orally treated with ASHMI, ASHMI(II), or vehicle (water). In a separate experiment, some RW sensitized mice were treated with dexamethasone before challenge. After RW challenge, airway hyperreactivity (AHR), total and differential bronchoalveolar lavage fluid leukocyte counts, lung histologic features, and bronchoalveolar lavage fluid cytokine and chemokine levels were assessed. RW stimulation of the murine macrophage cell line RAW264.7 was used to determine effects of ASHMI active compound ganoderic acid C1 (GAC1) on tumor necrosis factor ? (TNF-?) production and regulation of phosphorylated I?B and histone deacetylase 2 (HDAC2) levels.ASHMI and ASHMI(II) markedly reduced AHR, mucous production, neutrophilic inflammation, and TNF-?, interleukin 8, and interleukin 17 levels and decreased eosinophilic inflammation and TH2 responses in vivo (P < .01-.001 for all). GAC1 inhibited TNF-? production in RW-stimulated RAW264.7 cells in association with suppression of phosphorylated I?B and increased HDAC2 expression. Dexamethasone failed to reduce AHR and neutrophilic inflammation.ASHMI treatment was efficacious in a murine model of neutrophil-predominant asthma via modulation of innate chemokines, TH2 responses, nuclear factor-?B, and HDAC2. ASHMI, and/or its constituent GAC1, may be a valuable option for treating neutrophil-predominant asthma.

SUBMITTER: Srivastava KD

PROVIDER: S-EPMC4118772 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.

Srivastava Kamal D KD Dunkin David D Liu Changda C Yang Nan N Miller Rachel L RL Sampson Hugh A HA Li Xiu-Min XM

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20140401 4

<h4>Background</h4>Neutrophil-predominant asthma is less responsive to steroids and associated with poorer disease control. The effects of Antiasthma Simplified Herbal Medicine Intervention (ASHMI), a traditional Chinese medicine formula reported to be efficacious in asthmatic patients and murine asthma models, on neutrophil predominant asthma are unknown.<h4>Objective</h4>To determine the effects of standard ASHMI and refined formula ASHMI (ASHMI(II)) in a neutrophil-predominant murine model of ...[more]

PMID: 24679734

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Project description:BackgroundMaternal asthma is a risk factor for asthma in offspring; however, transmission of the risk for allergic asthma without direct offspring sensitization has not been explored.ObjectiveTo determine whether offspring from mothers with ovalbumin (OVA)-sensitized asthma would develop airway disease at first-ever exposure to OVA and whether preconception maternal treatment with the Antiasthma Simplified Herbal Medicine Intervention (ASHMI) or dexamethasone (DEX) could modify this risk in offspring.MethodsFemale BALB/c mice (F0) with OVA-induced asthma were generated using established protocols. Mice with asthma were treated with ASHMI, DEX, or water for 6 to 7 weeks. Naive mice served as controls. Subsequently, mice were mated. Twelve-day-old F1 offspring received 3 consecutive intranasal low- or high-dose OVA exposures without sensitization. Forty-eight hours later, airway inflammation, mucus hypersecretion, serum antibodies, and cytokines were evaluated.ResultsOffspring from OVA-sensitized mothers, but not naive mothers, showed eosinophilic and neutrophilic airway inflammation, and mucus hyperplasia after OVA exposure and he presence of OVA-specific IgG1 and IgG2a. Offspring of ASHMI- and DEX-treated mothers showed decreased airway inflammation and mucus hypersecretion after low-dose OVA (P < .05-.001 for the 2 comparisons vs offspring of OVA/Sham mothers). Offspring of ASHMI-treated, but not DEX-treated, mothers were protected after the high-dose OVA challenge (P < .05-.01 vs offspring OVA/Sham). Maternal ASHMI therapy was associated with increased IgG2a (P < .01 vs offspring of OVA/Sham mothers) and decreased bronchoalveolar lavage fluid CXCL-1 and eotaxin-1 levels (P < .01 and P < .05, respectively, vs offspring of OVA/Sham mothers).ConclusionOffspring of mothers with OVA-induced asthma developed airway inflammation and mucus to first-ever OVA exposure without prior sensitization. Maternal therapy with ASHMI was superior to DEX in decreasing offspring susceptibility to airway disease and could be a strategy to lower asthma prevalence.

Project description:BACKGROUND:Airway neutrophils are abundant in some children with severe asthma, but their functions are poorly understood. OBJECTIVE:To characterize that the inflammatory airway environment of children with neutrophil-predominant severe asthma promotes neutrophil survival and disrupts neutrophil-associated innate immune defenses. METHODS:Sixty-seven children with severe asthma refractory to high-dose inhaled corticosteroid treatment undergoing bronchoscopy with bronchoalveolar lavage (BAL) for clinical indications were stratified into neutrophil "high" versus "low" groups on the basis of BAL differential counts. Neutrophil activation markers, functional assays, and phenotyping studies were performed, as well as airway macrophage functional assays. Results were compared with those from children with moderate asthma treated with inhaled corticosteroids. RESULTS:Children with neutrophil-predominant severe asthma had increased markers of neutrophil activation/degranulation and a greater magnitude of airway proinflammatory cytokine and chemokine release. Primary neutrophils exposed to BAL of these children exhibited greater phagocytic capability and greater neutrophil extracellular trap formation, but a more impaired respiratory burst. Despite greater abundance of airway TGF-?1, the neutrophils were not more apoptotic. Instead, neutrophils had a highly proinflammatory phenotype associated with a number of surface markers that regulate neutrophil activation, recruitment/migration, and granule release. Airway macrophages from children with neutrophil-predominant severe asthma were also more proinflammatory with impaired phagocytosis and increased apoptosis. CONCLUSIONS:Children with neutrophil-predominant severe asthma have proinflammatory neutrophils with enhanced survival. Airway macrophages are also proinflammatory and dysfunctional and may contribute to global innate immune impairment. Therapies that target neutrophils and related inflammation may be warranted in this subset of children.

Dataset Information

Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.

Publications

Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.

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