CYP27A1-27-hydroxycholesterol axis in the respiratory system contributes to house dust mite-induced allergic airway inflammation

  • Ito Tatsunori
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Ichikawa Tomohiro
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Yamada Mitsuhiro
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Hashimoto Yuichiro
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Fujino Naoya
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Numakura Tadahisa
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Sasaki Yusaku
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Suzuki Ayumi
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Takita Katsuya
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Sano Hirohito
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Kyogoku Yorihiko
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Saito Takuya
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Koarai Akira
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Tamada Tsutomu
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
  • Sugiura Hisatoshi
    Department of Respiratory Medicine, Tohoku University Graduate School of Medicine

抄録

<p>Background: 27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma.</p><p>Methods: House dust mite (HDM) extract was intranasally administered to C57BL/6 mice and the expression of CYP27A1 in the airways was analyzed by immunostaining. The effect of pre-treatment with PBS or CYP27A1 inhibitors on the cell fraction in the bronchoalveolar lavage fluid (BALF) was analyzed in the murine model. In vitro, BEAS-2B cells were treated with HDM and the levels of CYP27A1 expression were examined. Furthermore, the effect of 27-HC on the expressions of E-cadherin and ZO-1 in the cells was analyzed. The amounts of RANTES and eotaxin from the 27-HC-treated cells were analyzed by ELISA.</p><p>Results: The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin.</p><p>Conclusions: The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production.</p>

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