期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 324, 期 3, 页码 1087-1094出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.09.157
关键词
outer membrane protein P6; mucin MUC5AC; TLR2; p38 MAPK; AP1; NF-kappa B
资金
- NCI NIH HHS [CA 24321] Funding Source: Medline
- NHLBI NIH HHS [HL 073309, HL 075602, HL 070293] Funding Source: Medline
- NIAID NIH HHS [AI 019641] Funding Source: Medline
- NIDCD NIH HHS [DC 004562, DC 005843] Funding Source: Medline
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.
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