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

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.

Keywords: Androgen-binding proteins; Fungal keratitis; Inflammation; Interleukin-1β; Lacrimal gland.

MeSH terms

  • Androgen-Binding Protein / genetics
  • Androgen-Binding Protein / metabolism*
  • Animals
  • Aspergillosis / genetics
  • Aspergillosis / metabolism*
  • Aspergillus fumigatus*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Keratitis / genetics
  • Keratitis / metabolism*
  • Lacrimal Apparatus / metabolism*
  • Male
  • Mice, Inbred C57BL

Substances

  • Androgen-Binding Protein
  • Cytokines