Preliminary evaluation of KYNA ameliorates neuronal pyroptosis induced by HIV-1 gp120

Backgrounds: HIV-associated neurocognitive disorders (HAND) are the common complications in the central nervous system (CNS), mainly causing HIV dementia and leading to serious social economic load. HIV-1 gp120, the envelope protein of HIV-1, has been confirmed to be an important virulence factor of HAND, and the expression levels of pyroptosis-related genes in the brains of HIV-1 gp120 transgenic mice are significantly increased. Several studies have confirmed the broad neuroprotective potential of Kynurenic acid(KYNA) as a derivative of tryptophan metabolism. Our previous study found that tryptophan-fed mice had significantly increased KYNA levels in the brain and ameliorated HIV-1 gp120-induced neurological damage, but the mechanism is still unclear. In this study, we initially investigated the protective effect of KYNA against gp120-induced neuronal pyroptosis. Methods and materials: Sy5y-SH cells were used as the neuronal model in this study and grouped into control, LPS(2.5µg/L)+ATP(5mM), HIV-1 gp120(5nM), KYNA(25µM), HIV-1 gp120+KYNA(5µM), and HIV-1 gp120+KYNA(25µM) groups. The cells in the HIV-1 gp120 group were treated with gp120 (5nM) for 24h, and the cells in the ATP group were pretreated with ATP for 6h and LPS for 1h. After the treatment, the cells were lysed with RIPA, and the protein suspension was collected. Immunofluorescence was used to detect the expression level of ASC in each group, and Western blot was used to detect the expression of pyroptosis-related proteins in each group. Results: Immunofluorescence assay showed that KYNA treated did not affect ASC expression. HIV-1 gp120 and LPS+ATP significantly enhanced ASC expression compared control and KYNA-treated groups (P