屋尘螨
炎症
CYP27A1
免疫学
免疫染色
支气管肺泡灌洗
医学
肺
过敏原
内分泌学
内科学
过敏
免疫组织化学
新陈代谢
作者
Tatsunori Ito,Tomohiro Ichikawa,Mitsuhiro Yamada,Yuichiro Hashimoto,Naoya Fujino,Tadahisa Numakura,Y. Sasaki,Ayumi Suzuki,Katsuya Takita,Hirohito Sano,Yorihiko Kyogoku,Takuya Saito,Akira Koarai,Tsutomu Tamada,Hisatoshi Sugiura
标识
DOI:10.1016/j.alit.2023.08.005
摘要
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. 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. 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. 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.
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