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

Ran Chen, Jae Hyang Lim, Hirofumi Jono, Xin Xing Gu, Young S. Kim, Carol B. Basbaum, Timothy F. Murphy, Jian Dong Li

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121 Scopus citations

Abstract

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 IKKβ-IκBα-NF-κB 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.

Original languageEnglish
Pages (from-to)1087-1094
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume324
Issue number3
DOIs
StatePublished - 19 Nov 2004

Bibliographical note

Funding Information:
We are grateful to Drs. J. Han and David Lim for kindly providing various reagents. This work was supported by Grants from National Institute of Health DC004562, DC005843, and HL070293 (to J.D. Li), CA24321 (to Y.S. Kim and J. Gum), HL073309 and HL075602 (to C. Basbaum), and AI019641 (to T.F. Murphy), and the Department of Veterans Affairs Medical Research Service (to J. Gum and Y.S. Kim).

Keywords

  • AP1
  • Mucin MUC5AC
  • NF-κB
  • Outer membrane protein P6
  • p38 MAPK
  • TLR2

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