Attenuated Airway Eosinophilic Inflammations in IL-38 Knockout Mouse Model

  • MATSUOKA MASANOBU
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • KAWAYAMA TOMOTAKA
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • TOMINAGA MASAKI
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • KAIEDA SHINJIRO
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • TOKUNAGA YOSHIHISA
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • KAKU YOICHIRO
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • IMAOKA HARUKI
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • KINOSHITA TAKASHI
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • OKAMOTO MASAKI
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine
  • AKIBA JUN
    Department of Diagnostic Pathology, Kurume University Hospital
  • HOSHINO TOMOAKI
    Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine

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Abstract

<p>Summary: Background: The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed. </p><p>Methods: The numbers of eosinophils and neutrophils, and levels of IL-5, IL-13 and IL-17A protein and mRNA in bronchoalveolar lavage fluid (BALF) and lung tissue were compared between wild-type (WT) and IL-38-KO mice after OVA sensitization and challenge. The effects of additional purified recombinant mouse (rm) IL-38 protein were investigated in the IL-38-KO murine asthma model. </p><p>Results: The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p<0.05). The number of airway eosinophils in IL-38-KO mice was significantly lower than in WT mice after OVA challenge (p<0.01). BALF analysis confirmed the lower number of airway eosinophils in IL-38-KO mice and showed that this was significantly associated with lower IL-5 protein levels (r=0.92, p<0.0001). However, the additional rm IL-38 protein did not neutralize airway eosinophilia in IL-38-KO mice. </p><p>Conclusion: IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction.</p>

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