Ga-Young Park
Gachon University, Korea
Title: E-BABE- Ester alkaloids from Cephalotaxus interfere with the type I interferon pathway
Biography
Biography: Ga-Young Park
Abstract
Inappropriate recognition of self-DNA contributes to interferonopathy and promotes autoimmune diseases like systemic lupus erythematosus (SLE) and chronic polyarthritis. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway plays an important role in production of inflammatory cytokines. To identify potential suppressors of STING-induced type I interferon (IFN) induction, 70% ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-β promoter activation. As a result, 70% ethanol extract of Cephalotaxus koreana specifically down-regulated STING-induced, but not TBK1- or IRF3-induced, IFN-β promoter activity. The compounds exerting inhibitory activity specifically against STING-mediated IFN-β promoter activation in 70% ethanol extract of Cephalotaxus koreana were identified as ester alkaloids, homoharringtonine and harringtonine. These two compounds inhibited 2’3’-cGAMP-induced IFN-stimulated gene expression and interaction between STING and TBK1. These suppressive effects were not observed with cephalotaxine devoid of the ester side-chain. Our data support the potential utility of homoharringtonine and harringtonine to treat STING-associated interferonopathy and autoimmune diseases