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

Research output: Contribution to journalArticlepeer-review

117 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

Keywords

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

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