GSDMD, an executor of pyroptosis, is involved in IL-1 β secretion in Aspergillus fumigatus keratitis.

GSDMD, an executor of pyroptosis, is involved in IL-1β secretion in Aspergillus fumigatus keratitis.
Exp Eye Res. 2020 Dec 03;:108375
Authors: Zhao W, Yang H, Lyu L, Zhang J, Xu Q, Jiang N, Liu G, Wang L, Yan H, Che C
Abstract
The protein GSDMD is an important performer of pyroptosis and a universal substrate for the inflammatory caspase. However, the role and regulatory mechanism of GSDMD in Aspergillus fumigatus keratitis is remains unknown. Here we detected GSDMD protein in the cornea of normal and fungal-infected C57BL/6 mice. Human corneal epithelial cell (HCECs) were preincubated with a hydrochloride solution (IFNR inhibitor), ruxolitinib (JAK/STAT inhibitor), belnacasan (caspase-1 inhibitor) before infection with A. fumigatus conidia. Mice corneas were infected with Aspergillus fumigatus after pretreatment of GSDMD siRNA via subconjunctival injection. After, samples were harvested at specific time points and the expression of GSDMD and IL-1β was assessed by PCR, Western blot and immunofluorescence staining. Compared with the control group, we observed that the expression of GSDMD in fungal-infected mice cornea was significantly increased. After pretreatment with IFNR, JAK/STAT and caspase-1 inhibitors before fungal infection, the expression of GSDMD was significantly inhibited compared to the DMSO control in HCECs. Moreover, the GSDMD siRNA treatment have significantly weaken corneal inflammatory response, decreasing the pro...

Source: Experimental Eye Research - December 3, 2020 Category: Opthalmology Authors: Zhao W, Yang H, Lyu L, Zhang J, Xu Q, Jiang N, Liu G, Wang L, Yan H, Che C Tags: Exp Eye Res Source Type: research