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泪液雄激素结合蛋白可预防烟曲霉菌角膜炎在小鼠模型中的发生。

Lacrimal androgen-binding proteins protect against Aspergillus fumigatus keratitis in mice.

机构信息

Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

Gout Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

出版信息

Int Immunopharmacol. 2020 Nov;88:106940. doi: 10.1016/j.intimp.2020.106940. Epub 2020 Sep 8.

Abstract

AIM

To clarify the regulatory mechanisms of lacrimal androgen-binding proteins (ABPs) in mice with keratitis caused by Aspergillus fumigatus (A. fumigatus).

METHODS

Mouse models of A. fumigatus keratitis were established. Lacrimal glands were removed after 24 h for general and histological comparison. Lacrimal ABPs were detected by qRT-PCR and quantitative proteomic analysis, or were detected by qRT-PCR after subconjunctival or lacrimal gland injection with dexamethasone. Unique inflammatory factors were detected by qRT-PCR, Western blot and/or immunofluorescence. Interleukin-1β (IL-1β) was injected into the lacrimal gland to explore the relationship between IL-1β and lacrimal ABPs.

RESULTS

The lacrimal glands of mice with fungal keratitis were larger than normal mice and these structures became disorganized. Moreover, the expression of ABP ε and ABP δ were increased. Subconjunctival injection with dexamethasone could reduce the size of the lacrimal gland and increase the expression of ABP ε and ABP δ, while lacrimal gland injection with dexamethasone had no obvious effects. The expression of IL-1β in the lacrimal gland of mice with A. fumigatus keratitis was increased. When IL-1β was injected into the lacrimal gland, the lacrimal gland enlarged and the expression of ABP ε and ABP δ decreased.

CONCLUSION

Lacrimal glands contributed to protection in fungal keratitis, which was not due to the involvement of inflammatory cells in mice. ABP δ and ABP ε of mice were involved in reducing the severity of corneal damage in mice with A. fumigatus keratitis. Moreover, the expression of IL-1β and ABP δ and ABP ε were intrinsically linked.

摘要

目的

阐明曲霉菌(Aspergillus fumigatus,A. fumigatus)角膜炎小鼠中泪腺雄激素结合蛋白(androgen-binding protein,ABP)的调控机制。

方法

建立 A. fumigatus 角膜炎小鼠模型。造模后 24 h 取泪腺进行大体和组织学比较。采用 qRT-PCR 和定量蛋白质组学分析检测泪腺 ABP,或通过结膜下或泪腺注射地塞米松检测泪腺 ABP。采用 qRT-PCR、Western blot 和/或免疫荧光检测独特的炎症因子。通过向泪腺注射白细胞介素-1β(interleukin-1β,IL-1β),探索 IL-1β与泪腺 ABP 之间的关系。

结果

真菌性角膜炎小鼠的泪腺大于正常小鼠,结构紊乱。ABPε和 ABPδ表达增加。结膜下注射地塞米松可减少泪腺大小并增加 ABPε和 ABPδ的表达,而泪腺注射地塞米松则无明显作用。A. fumigatus 角膜炎小鼠泪腺中 IL-1β表达增加。向泪腺注射 IL-1β时,泪腺增大,ABPε和 ABPδ的表达减少。

结论

泪腺参与了真菌性角膜炎的保护作用,这与小鼠炎症细胞的参与无关。ABPδ和 ABPε参与了减轻 A. fumigatus 角膜炎小鼠角膜损伤的严重程度。此外,IL-1β和 ABPδ和 ABPε的表达存在内在联系。

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