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.
Int Immunopharmacol. 2020 Nov;88:106940. doi: 10.1016/j.intimp.2020.106940. Epub 2020 Sep 8.
To clarify the regulatory mechanisms of lacrimal androgen-binding proteins (ABPs) in mice with keratitis caused by Aspergillus fumigatus (A. fumigatus).
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.
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.
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.
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。
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。
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。
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。