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

Autor:	Ito T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Ichikawa T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: ichikawa@rm.med.tohoku.ac.jp., Yamada M; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Hashimoto Y; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Fujino N; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Numakura T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Sasaki Y; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Suzuki A; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Takita K; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Sano H; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Kyogoku Y; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Saito T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Koarai A; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Tamada T; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan., Sugiura H; Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Jazyk:	angličtina
Zdroj:	Allergology international : official journal of the Japanese Society of Allergology [Allergol Int] 2024 Jan; Vol. 73 (1), pp. 151-163. Date of Electronic Publication: 2023 Aug 20.
DOI:	10.1016/j.alit.2023.08.005
Abstrakt:	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. 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. 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. 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. (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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