Experimental Study On The Role Of KAT5 In The Pathogenesis Of Allergic Conjunctivitis

Objective:To explore the role of lysine acetyltransferase 5(KAT5)in the pathogenesis of allergic conjunctivitis(AC).Methods:To explore the role and mechanism of KAT5 in the pathogenesis of AC by establishing a mouse model of AC.Result:The clinical score,vascular permeability,total IgE,ovalbumin(OVA)specific IgE and Ig G1/Ig G2 a expression of AC mice were all increased.The overexpression of KAT5 could further enhance these manifestations,while the KAT5 inhibitor NU9056 weakened these manifestations.There was eosinophil infiltration in the eyes of AC mice.Overexpression of KAT5 could further promote eosinophil infiltration in the eyes of AC mice,while NU9056 could inhibit its infiltration.The expression of eosinophil chemokine,chemokine RANTES and inflammatory factors,including IL-4,IL-13,IL-5 and IL-10,was up-regulated in the eyes of AC mice,and the over-expression of KAT5 increased this trend,while NU9056 reversed this trend.The infiltration of CD11c+dendritic cells and CD4+T cells in the conjunctiva of AC mice increased,and the overexpression of KAT5 enhanced this effect,but NU9056 inhibited this effect.Through KAT5 gene knockout mice,we found that the infiltration of conjunctival eosinophils in AC mice was inhibited.At the same time,KAT5 gene knockout inhibited the up-regulation of Eoaxin and RANTES expression in the eyes of AC mice.The increase of IL-4,IL-13 and IL-5 levels in the eyes of AC mice and the decrease of IL-10 levels were also reversed by the knockout of KAT5 gene.The infiltration of CD11c+dendritic cells and CD4+T cells in the conjunctiva of AC mice was also reversed by KAT5 gene knockout.Through the study of the mechanism of KAT5 action,it was found that the expression of PI3 K and Akt in AC mice increased,and the overexpression of KAT5 promoted this trend,while NU9056 inhibited this change.Similarly,the level of H3K27 ac in AC mice was induced to increase,while the overexpression of KAT5 promoted this trend,and NU9056 reversed this change.Moreover,in AC mice,the enrichment of KAT5 and H3K27 ac on the PI3 K promoter was significantly increased,and the overexpression of KAT5 further enhanced their enrichment in AC mice.At the same time,the PI3K/AKT signal transduction inhibitor LY294002 reversed various changes caused by KAT5 overexpression in the AC model in vivo.Conclusion:KAT5 enhances the inflammatory response in vivo through PI3K/AKT pathway,and then induces AC.