Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKK beta-I kappa B alpha-NF-kappa B signaling pathways

Chen R; Lim JH; Jono H; Gu XX; Kim YS; Basbaum CB; Murphy TF; Li JD

Biochemical and Biophysical Research Communications, Vol.324, No.3, 1087-1094, 2004

DOI10.1016/j.bbrc.2004.09.157 Export Citation

Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKK beta-I kappa B alpha-NF-kappa B signaling pathways

Chen R, Lim JH, Jono H, Gu XX, Kim YS, Basbaum CB, Murphy TF, Li JD

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.

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