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

Department of Microbiology

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

122 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 - 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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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

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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}",

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). ",

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month = nov,

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

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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

N1 - 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).

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.

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KW - Mucin MUC5AC

KW - NF-κB

KW - Outer membrane protein P6

KW - p38 MAPK

KW - TLR2

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U2 - 10.1016/j.bbrc.2004.09.157

DO - 10.1016/j.bbrc.2004.09.157

M3 - Article

C2 - 15485666

AN - SCOPUS:5444253271

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

Bibliographical note

Keywords

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