Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disinteg...Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.展开更多
目的研究去整合素金属蛋白酶10(a disintegrin and metalloprotease 10,ADAM10)在喉癌中的表达及其临床意义。方法采用实时荧光定量RT-PCR法(n=21)与组织芯片免疫组化法(n=62)检测ADAM10在喉癌组织与正常黏膜组织中的表达情况,并分析其...目的研究去整合素金属蛋白酶10(a disintegrin and metalloprotease 10,ADAM10)在喉癌中的表达及其临床意义。方法采用实时荧光定量RT-PCR法(n=21)与组织芯片免疫组化法(n=62)检测ADAM10在喉癌组织与正常黏膜组织中的表达情况,并分析其差异。结果实时荧光定量RT-PCR结果显示喉癌组织中ADAM10表达显著高于正常黏膜组织中的表达(P<0.001),其倍数为2.691±1.568。组织芯片结果显示ADAM10在喉癌组织中阳性面积百分比为15.243±7.824,在正常黏膜组织中则为1.887±1.918,喉癌组织中ADAM10的表达量高于正常黏膜组织(P<0.001)。ADAM10的表达与组织学分级相关,与其他临床参数无关。结论 ADAM10在喉癌组织中有高表达,其表达与肿瘤组织学分级相关。展开更多
基金supported by the National Natural Science Foundation of China(U22A20523,32172912,and 32102722)the Interdisciplinary Integration and Innovation Project of Jilin University(JLUXKJC2021QZ04)。
文摘Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.
