LY294002 attenuates inflammatory response in endotoxin-induced uveitis by downregulating JAK3 and inactivating the PI3K/Akt signaling.

Xinyang Wu, Lijun Pu, Wei Chen, Qi Zhao, Geping Wu, Di Li, Hongyan Zhu

Immunopharmacology and immunotoxicology 2022 Aug

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Uveitis is a prevalent inflammatory eye disease that damages the vision of patients and even leads to blindness. LY294002, an inhibitor of PI3K, was reported to suppress the inflammation and alleviate the progression of many diseases. However, the function of LY294002 in uveitis is unclear. This study aimed to explore the function of LY294002 in endotoxin-induced uveitis (EIU). EIU rat models were established via a single intravitreal injection of LPS. At 24 h after LPS injection, the rats received LY294002 treatment for 14 days. The histopathology was observed by H&E staining. The concentration of proinflammatory cytokines in aqueous humor was tested by ELISA. The expression of proinflammatory cytokines in the iris ciliary body (ICB) and retina of EIU rats were detected by RT-qPCR. JAK3, PI3K, and Akt expression were assessed by RT-qPCR and western blotting. Translocation of Akt in rat retinal Müller cells (rMC-1) was evaluated by immunofluorescence staining. LY294002 alleviated ocular inflammation and decreased inflammatory cell infiltration in the anterior chamber, iris, ciliary body, vitreous cavity, and retina of EIU rats. LY294002 decreased the concentration of proinflammatory cytokines INF-γ, IL-17, IL-6, TNF-α, and IL-1β in aqueous humor and their expression in the ICB and retina of EIU rats. LY294002 downregulated JAK3 expression in EIU rats. LY294002 inhibited p-PI3K and p-Akt expression in EIU rats and restrained Akt translocation from cytoplasm to cell membrane in LPS-treated rMC-1 cells. LY294002 ameliorates inflammation in EIU by downregulating JAK3 and inactivating the PI3K/Akt signaling.

Citation

Xinyang Wu, Lijun Pu, Wei Chen, Qi Zhao, Geping Wu, Di Li, Hongyan Zhu. LY294002 attenuates inflammatory response in endotoxin-induced uveitis by downregulating JAK3 and inactivating the PI3K/Akt signaling. Immunopharmacology and immunotoxicology. 2022 Aug;44(4):510-518