不可分型流感嗜血杆菌脂蛋白P6通过TLR2-TAK1依赖的p38丝裂原活化蛋白激酶-活化蛋白1和IKKβ-IκBα-核因子κB信号通路诱导MUC5AC黏蛋白转录。
Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKbeta-IkappaBalpha-NF-kappaB signaling pathways.
作者信息
Chen Ran, Lim Jae Hyang, Jono Hirofumi, Gu Xin-Xing, Kim Young S, Basbaum Carol B, Murphy Timothy F, Li Jian-Dong
机构信息
Gonda Department of Cell and Molecular Biology, House Ear Institute, University of Southern California, Los Angeles, CA 90057, USA.
出版信息
Biochem Biophys Res Commun. 2004 Nov 19;324(3):1087-94. doi: 10.1016/j.bbrc.2004.09.157.
Mucin overproduction is a hallmark of nontypeable Haemophilus influenzae (NTHi) infections. The molecular mechanisms underlying up-regulation of mucin in NTHi infections especially during the initial phase remain unknown. Here we show that P6, a 16-kDa outer membrane lipoprotein well conserved in NTHi, up-regulates MUC5AC mucin gene transcription in vitro and in vivo. Moreover, P6 induces MUC5AC transcription via TLR2-MyD88-IRAK1-TRAF6-TAK1-dependent p38 MAPK-AP1 and IKKbeta-IkappaBalpha-NF-kappaB signaling pathways. This study may bring new insights into the molecular pathogenesis of NTHi-induced infections and lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections.
粘蛋白过度产生是不可分型流感嗜血杆菌（NTHi）感染的一个标志。NTHi感染尤其是在初始阶段粘蛋白上调的分子机制仍不清楚。在此我们表明，P6是一种在NTHi中高度保守的16 kDa外膜脂蛋白，在体外和体内均可上调MUC5AC粘蛋白基因转录。此外，P6通过TLR2-MyD88-IRAK1-TRAF6-TAK1依赖的p38 MAPK-AP1和IKKβ-IκBα-NF-κB信号通路诱导MUC5AC转录。本研究可能为NTHi诱导感染的分子发病机制带来新见解，并为抑制NTHi感染患者粘蛋白过度产生带来新的治疗干预措施。
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