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Enhanced airway inflammation and decreased subepithelial fibrosis in interleukin 6-deficient mice following chronic exposure to aerosolized antigen

Authors

  • Z. Qiu,

    1. Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, Kanazawa, Japan,
    2. Department of Respiratory Medicine, Affiliated Tongji Hospital of Tongji University, Shanghai, China
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  • M. Fujimura,

    1. Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, Kanazawa, Japan,
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  • K. Kurashima,

    1. Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, Kanazawa, Japan,
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  • S. Nakao,

    1. Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, Kanazawa, Japan,
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  • N. Mukaida

    1. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
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Dr Masaki Fujimura, Respiratory Medicine, Cellular Transplantation Biology, Kanazawa Graduate University School of Medicine, 13-1 Takara-machi, 920-8641 Kanazawa, Japan.
E-mail: fujimura@med3.m.kanazawa-u.ac.jp

Summary

Background Airway inflammation and remodelling are characteristic features of chronic asthma.

Objective To elucidate the role of interleukin (IL)-6 in airway responses to chronic antigen exposure.

Methods We compared airway inflammation, subepithelial collagen deposition, cytokine mRNA expression, and airway responsiveness between IL-6-deficient and wild-type (WT) mice following sensitization and repeated exposure to ovalbumin (OVA) three times a week for 8 weeks.

Results The repeated exposure to OVA induced infiltration of eosinophils, neutrophils, and lymphocytes into the airway, and caused thickening of the basement membrane and subepithelial fibrosis. IL-6-deficient mice exhibited more pronounced infiltration of these cells, a thinner basement membrane, and decreased subepithelial fibrosis, compared with WT mice. The repeated OVA exposure increased expression of IL-4, IL-13, eotaxin, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 mRNA in WT mice. Among these factors, expression of IL-13 and MCP-1 mRNA was further enhanced in IL-6-deficient mice, compared with WT mice. However, both WT and IL-6-deficient mice exhibited similar levels of airway responsiveness to increasing doses of methacholine, even after repeated exposure to OVA.

Conclusion These results suggest that IL-6 has dual roles in the chronic phase of asthma: down-regulation of inflammatory cell infiltration and enhancement of airway remodelling.

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