Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK

Kensei Komatsu; Hirofumi Jono; Jae Hyang Lim; Akira Imasato; Haidong Xu; Hirofumi Kai; Chen Yan; Jian Dong Li

doi:10.1016/j.bbrc.2008.10.091

Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK

Kensei Komatsu, Hirofumi Jono, Jae Hyang Lim, Akira Imasato, Haidong Xu, Hirofumi Kai, Chen Yan, Jian Dong Li

Department of Microbiology

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

28 Scopus citations

Abstract

Glucocorticoids are highly effective in the control of many inflammatory and immune diseases. Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, the molecular basis for the inhibitory effect of glucocorticoids on mucin overproduction, a hallmark of chronic respiratory diseases, still remains unclear. Here we show that glucocorticoids markedly inhibit up-regulation of MUC5AC induced by NTHi, a major human bacterial pathogen causing chronic obstructive pulmonary disease and otitis media. Inhibition of NTHi-induced MUC5AC expression by dexamethasone occurs at the level of p38 MAPK via glucocorticoid receptor. Moreover, glucocorticoids up-regulate MKP-1 expression, which in turn leads to p38 dephosphorylation and the subsequent inhibition of NTHi-induced MUC5AC expression. These studies provide new insight into the molecular mechanism underlying glucocorticoid therapy and may lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections.

Original language	English
Pages (from-to)	763-768
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	377
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2008.10.091
State	Published - 19 Dec 2008

Bibliographical note

Funding Information:
This work was supported by grants from National Institute of Health DC004562 and DC005843 (to JDL), P01 HL077789 and RO1 HL088400 (to C. Yan). Dr. Yan is a recipient of Established Investigator Awards of American Heart Association (0740021 N).

Keywords

Glucocorticoids
MKP-1
MUC5AC mucin
Nontypeable Haemophilus influenzae
p38 MAPK

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10.1016/j.bbrc.2008.10.091

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@article{5ca82a6918b240b0aa8e011f9a488930,

title = "Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK",

abstract = "Glucocorticoids are highly effective in the control of many inflammatory and immune diseases. Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, the molecular basis for the inhibitory effect of glucocorticoids on mucin overproduction, a hallmark of chronic respiratory diseases, still remains unclear. Here we show that glucocorticoids markedly inhibit up-regulation of MUC5AC induced by NTHi, a major human bacterial pathogen causing chronic obstructive pulmonary disease and otitis media. Inhibition of NTHi-induced MUC5AC expression by dexamethasone occurs at the level of p38 MAPK via glucocorticoid receptor. Moreover, glucocorticoids up-regulate MKP-1 expression, which in turn leads to p38 dephosphorylation and the subsequent inhibition of NTHi-induced MUC5AC expression. These studies provide new insight into the molecular mechanism underlying glucocorticoid therapy and may lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections.",

keywords = "Glucocorticoids, MKP-1, MUC5AC mucin, Nontypeable Haemophilus influenzae, p38 MAPK",

author = "Kensei Komatsu and Hirofumi Jono and Lim, {Jae Hyang} and Akira Imasato and Haidong Xu and Hirofumi Kai and Chen Yan and Li, {Jian Dong}",

note = "Funding Information: This work was supported by grants from National Institute of Health DC004562 and DC005843 (to JDL), P01 HL077789 and RO1 HL088400 (to C. Yan). Dr. Yan is a recipient of Established Investigator Awards of American Heart Association (0740021 N).",

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Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK. / Komatsu, Kensei; Jono, Hirofumi; Lim, Jae Hyang et al.
In: Biochemical and Biophysical Research Communications, Vol. 377, No. 3, 19.12.2008, p. 763-768.

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

TY - JOUR

T1 - Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK

AU - Komatsu, Kensei

AU - Jono, Hirofumi

AU - Lim, Jae Hyang

AU - Imasato, Akira

AU - Xu, Haidong

AU - Kai, Hirofumi

AU - Yan, Chen

AU - Li, Jian Dong

N1 - Funding Information: This work was supported by grants from National Institute of Health DC004562 and DC005843 (to JDL), P01 HL077789 and RO1 HL088400 (to C. Yan). Dr. Yan is a recipient of Established Investigator Awards of American Heart Association (0740021 N).

PY - 2008/12/19

Y1 - 2008/12/19

N2 - Glucocorticoids are highly effective in the control of many inflammatory and immune diseases. Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, the molecular basis for the inhibitory effect of glucocorticoids on mucin overproduction, a hallmark of chronic respiratory diseases, still remains unclear. Here we show that glucocorticoids markedly inhibit up-regulation of MUC5AC induced by NTHi, a major human bacterial pathogen causing chronic obstructive pulmonary disease and otitis media. Inhibition of NTHi-induced MUC5AC expression by dexamethasone occurs at the level of p38 MAPK via glucocorticoid receptor. Moreover, glucocorticoids up-regulate MKP-1 expression, which in turn leads to p38 dephosphorylation and the subsequent inhibition of NTHi-induced MUC5AC expression. These studies provide new insight into the molecular mechanism underlying glucocorticoid therapy and may lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections.

AB - Glucocorticoids are highly effective in the control of many inflammatory and immune diseases. Despite the importance of glucocorticoids in suppressing immune and inflammatory responses, the molecular basis for the inhibitory effect of glucocorticoids on mucin overproduction, a hallmark of chronic respiratory diseases, still remains unclear. Here we show that glucocorticoids markedly inhibit up-regulation of MUC5AC induced by NTHi, a major human bacterial pathogen causing chronic obstructive pulmonary disease and otitis media. Inhibition of NTHi-induced MUC5AC expression by dexamethasone occurs at the level of p38 MAPK via glucocorticoid receptor. Moreover, glucocorticoids up-regulate MKP-1 expression, which in turn leads to p38 dephosphorylation and the subsequent inhibition of NTHi-induced MUC5AC expression. These studies provide new insight into the molecular mechanism underlying glucocorticoid therapy and may lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with NTHi infections.

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Glucocorticoids inhibit nontypeable Haemophilus influenzae-induced MUC5AC mucin expression via MAPK phosphatase-1-dependent inhibition of p38 MAPK

Abstract

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Keywords

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