Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKbeta-IkappaBalpha-NF-kappaB signaling pathways

Biochem Biophys Res Commun. 2004 Nov 19;324(3):1087-94. doi: 10.1016/j.bbrc.2004.09.157.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Membrane / metabolism
  • Cells, Cultured
  • DNA Primers / chemistry
  • Enzyme Activation
  • Haemophilus influenzae
  • Humans
  • I-kappa B Kinase
  • I-kappa B Proteins / metabolism*
  • Lipoproteins / chemistry*
  • Luciferases / metabolism
  • MAP Kinase Kinase Kinases / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Mucin 5AC
  • Mucins / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Plasmids / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Transcription Factor AP-1 / metabolism*
  • Transcription, Genetic*
  • Transfection
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • DNA Primers
  • I-kappa B Proteins
  • Lipoproteins
  • MUC5AC protein, human
  • Membrane Glycoproteins
  • Muc5ac protein, mouse
  • Mucin 5AC
  • Mucins
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Receptors, Cell Surface
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptors
  • Transcription Factor AP-1
  • NF-KappaB Inhibitor alpha
  • Luciferases
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • Chuk protein, mouse
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7