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

LY294002 通过下调 JAK3 和抑制 PI3K/Akt 信号来减轻内毒素诱发的葡萄膜炎的炎症反应

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

Conclusion

LY294002 ameliorates inflammation in EIU by downregulating JAK3 and inactivating the PI3K/Akt signaling.

Methods

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.

Objective

This study aimed to explore the function of LY294002 in endotoxin-induced uveitis (EIU). Materials and

Results

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.

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