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Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma
Journal article   Peer reviewed

Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma

Melissa E Munroe, Thomas R Businga, Joel N Kline and Gail A Bishop
The Journal of immunology (1950), Vol.185(9), pp.5586-5597
11/01/2010
DOI: 10.4049/jimmunol.1000630
PMCID: PMC3197781
PMID: 20889543

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Abstract

Chronic airway inflammation is a hallmark of asthma, an immune-based disease with great societal impact. Honokiol (HNK), a phenolic neurotransmitter receptor (γ-aminobutyric acid type A) agonist purified from magnolia, has anti-inflammatory properties, including stabilization of inflammation in experimentally induced arthritis. The present study tested the prediction that HNK could inhibit the chronic inflammatory component of allergic asthma. C57BL/6 mice sensitized to and challenged with OVA had increased airway hyperresponsiveness to methacholine challenge and eosinophilia compared with naive controls. HNK-treated mice showed a reduction in airway hyperresponsiveness as well as a significant decrease in lung eosinophilia. Histopathology studies revealed a marked drop in lung inflammation, goblet cell hyperplasia, and collagen deposition with HNK treatment. Ag recall responses from HNK-treated mice showed decreased proinflammatory cytokines in response to OVA, including TNF-α-, IL-6-, Th1-, and Th17-type cytokines, despite an increase in Th2-type cytokines. Regulatory cytokines IL-10 and TGF-β were also increased. Assessment of lung homogenates revealed a similar pattern of cytokines, with a noted increase in the number of FoxP3(+) cells in the lung. HNK was able to alter B and T lymphocyte cytokine secretion in a γ-aminobutyric acid type A-dependent manner. These results indicate that symptoms and pathology of asthma can be alleviated even in the presence of increased Th2 cytokines and that neurotransmitter agonists such as HNK have promise as a novel class of anti-inflammatory agents in the treatment of chronic asthma.
Lung - pathology Enzyme-Linked Immunosorbent Assay Mice, Inbred C57BL Th2 Cells - immunology Hypersensitivity - complications Asthma - drug therapy Biphenyl Compounds - therapeutic use Hypersensitivity - drug therapy Th2 Cells - drug effects Lignans - therapeutic use Animals Eosinophilia - immunology Lung - drug effects Asthma - immunology Fluorescent Antibody Technique Anti-Inflammatory Agents - therapeutic use Female Mice Cytokines - biosynthesis Lung - immunology Cytokines - immunology Disease Models, Animal

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