Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKβ-IκBα-NF-κB signaling pathways

被引：114

作者：

Chen, R

Lim, JH

Jono, H

Gu, XX

Kim, YS

Basbaum, CB

Murphy, TF

Li, JD ^{[1
]}

机构：

[1] Univ So Calif, House Ear Inst, Gonda Dept Cell & Mol Biol, Los Angeles, CA 90057 USA

[2] Univ So Calif, Dept Otolaryngol, Los Angeles, CA 90057 USA

[3] Natl Inst Deafness & Other Commun Disorders, Immunol Lab, Rockville, MD 20850 USA

[4] Univ Calif San Francisco, Vet Affairs Med Ctr, Gastrointestinal Res Lab, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA

[8] SUNY Buffalo, Div Infect Dis, Buffalo, NY 14215 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 324卷 / 03期

关键词：

outer membrane protein P6; mucin MUC5AC; TLR2; p38; MAPK; AP1; NF-kappa B;

D O I：

10.1016/j.bbrc.2004.09.157

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：1087 / 1094

页数：8

共 31 条

[31] Novel cytoplasmic proteins of nontypeable Haemophilus influenzae up-regulate human MUC5AC mucin transcription via a positive p38 mitogen-activated protein kinase pathway and a negative phosphoinositide 3-kinase-Akt pathway. [J].

Wang, BN ;

Lim, DJ ;

Han, JH ;

Kim, YS ;

Basbaum, CB ;

Li, JD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (02) :949-957

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