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

doi:10.1016/j.bbrc.2004.09.157

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

Medicine

University of Southern California
National Institutes of Health
University of California at San Francisco

Research output: Contribution to journal › Article › peer-review

131 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 language	English
Pages (from-to)	1087-1094
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	324
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2004.09.157
State	Published - Nov 19 2004

Keywords

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

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10.1016/j.bbrc.2004.09.157

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Chen, R., Lim, J. H., Jono, H., Gu, X. X., Kim, Y. S., Basbaum, C. B., Murphy, T. F., & Li, J. D. (2004). Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKβ- IκBα-NF-κB signaling pathways. Biochemical and Biophysical Research Communications, 324(3), 1087-1094. https://doi.org/10.1016/j.bbrc.2004.09.157

@article{ce86d1c9117b4b558f5a267811082d6d,

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

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.",

keywords = "AP1, Mucin MUC5AC, NF-κB, Outer membrane protein P6, p38 MAPK, TLR2",

author = "Ran Chen and Lim, \{Jae Hyang\} and Hirofumi Jono and Gu, \{Xin Xing\} and Kim, \{Young S.\} and Basbaum, \{Carol B.\} and Murphy, \{Timothy F.\} and Li, \{Jian Dong\}",

year = "2004",

month = nov,

day = "19",

doi = "10.1016/j.bbrc.2004.09.157",

language = "English",

volume = "324",

pages = "1087--1094",

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Chen, R, Lim, JH, Jono, H, Gu, XX, Kim, YS, Basbaum, CB, Murphy, TF & Li, JD 2004, 'Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKβ- IκBα-NF-κB signaling pathways', Biochemical and Biophysical Research Communications, vol. 324, no. 3, pp. 1087-1094. https://doi.org/10.1016/j.bbrc.2004.09.157

Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKβ- IκBα-NF-κB signaling pathways. / Chen, Ran; Lim, Jae Hyang; Jono, Hirofumi et al.
In: Biochemical and Biophysical Research Communications, Vol. 324, No. 3, 19.11.2004, p. 1087-1094.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Nontypeable Haemophilus influenzae lipoprotein P6 induces MUC5AC mucin transcription via TLR2-TAK1-dependent p38 MAPK-AP1 and IKKβ- IκBα-NF-κB signaling pathways

AU - Chen, Ran

AU - Lim, Jae Hyang

AU - Jono, Hirofumi

AU - Gu, Xin Xing

AU - Kim, Young S.

AU - Basbaum, Carol B.

AU - Murphy, Timothy F.

AU - Li, Jian Dong

PY - 2004/11/19

Y1 - 2004/11/19

N2 - 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.

AB - 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.

KW - AP1

KW - Mucin MUC5AC

KW - NF-κB

KW - Outer membrane protein P6

KW - p38 MAPK

KW - TLR2

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SN - 0006-291X

VL - 324

SP - 1087

EP - 1094

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

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

Abstract

Keywords

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