Cargando…
IFN-γ Facilitates Corneal Epithelial Cell Pyroptosis Through the JAK2/STAT1 Pathway in Dry Eye
PURPOSE: To investigate the effect of gamma interferon (IFN-γ) on corneal epithelial pyroptosis in an experimental dry eye (DE) model and explore the underlying molecular mechanisms. METHODS: Experimental DE was established in adult wild-type (WT) C57BL/6 mice and Ifng-knockout mice on a C57BL/6 bac...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064915/ https://www.ncbi.nlm.nih.gov/pubmed/36988949 http://dx.doi.org/10.1167/iovs.64.3.34 |
Sumario: | PURPOSE: To investigate the effect of gamma interferon (IFN-γ) on corneal epithelial pyroptosis in an experimental dry eye (DE) model and explore the underlying molecular mechanisms. METHODS: Experimental DE was established in adult wild-type (WT) C57BL/6 mice and Ifng-knockout mice on a C57BL/6 background by subcutaneous injection of scopolamine (1.5 mg/0.3 mL, three times per day) and exposure to desiccating stress. An immortalized human corneal epithelial cell line (HCE-T) was treated with IFN-γ under hyperosmolar conditions. Corneal epithelial defects, tear production, and conjunctival goblet cells were detected by fluorescein sodium staining, the phenol red cotton test, and periodic acid-Schiff staining. The mRNA expression was measured by quantitative real-time PCR. Changes in protein expression were analyzed by Western blotting and immunofluorescence staining. Cell Counting Kit-8 and lactate dehydrogenase assays and in situ TUNEL staining were used to assess cell death. RESULTS: The expression of IFNG and its related genes was increased in the corneas of DE mice, whereas genetic deletion of Ifng ameliorated desiccating stress-induced dry eye symptoms. We further found that IFN-γ activated the JAK2/STAT1 signaling pathway inducing corneal epithelial pyroptosis. Topical application of a STAT1 inhibitor in vivo or siRNA targeting STAT1 in vitro suppressed pyroptosis of corneal epithelial cells. In addition, the production of reactive oxygen species (ROS) was elevated in DE, and a reduction in excessive ROS release prevented pyroptosis. CONCLUSIONS: The increase in IFN-γ participates in the pathogenesis of dry eye and promotes corneal epithelial pyroptosis by activating the JAK2/STAT1 signaling pathway. Oxidative stress might be in downstream of JAK2/STAT1, thereby contributing to pyroptosis. |
---|