Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells.

Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells. Research Abstract Details 

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Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells. Abstract Text:

Tomoyuki Fujisawa,Kyotaro Ide,Michael J Holtzman,Takafumi Suda,Kenichiro Suzuki,Shigeki Kuroishi,Kingo Chida,Hirotoshi Nakamura,

Background and objective: IL-13 has been shown to play a pivotal role in mucous cell metaplasia, which is an important feature of the pathogenesis of asthma. However, the signalling pathways evoked by IL-13 in airway epithelial cells remain unclear. This study investigated the signalling mechanism of IL-13-induced mucous cell metaplasia in primary cultures of mouse tracheal epithelial cells (mTEC). Methods: mTEC were cultured in an air-liquid interface system in the presence or absence of IL-13. Goblet cell hyperplasia was evaluated quantitatively by immunofluorescent staining for MUC5AC, which is a major component of airway mucins. Western blotting was used to assess activation of the signalling molecules, signal transducer and activator of transcription 6 (STAT6), p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2. MUC5AC gene expression was measured by RT-PCR. Results: IL-13 induced mucous cell metaplasia for 7-14 days in mTEC. IL-13 phosphorylated STAT6 within 20 min, whereas it induced delayed phosphorylation of p38 MAPK 36-48 h after stimulation. In contrast, ERK1/2 was constantly activated and was not enhanced by IL-13. An inhibitor of p38 MAPK (SB202190) suppressed mucous cell differentiation in a concentration-dependent manner. In STAT6 knockout mice, IL-13 failed to induce mucous cell metaplasia and activate p38 MAPK. Cycloheximide also diminished activation of p38 MAPK and induction of MUC5AC mRNA expression by IL-13. Conclusions: The p38 MAPK pathway is involved in IL-13-induced mucous cell metaplasia and MUC5AC mRNA regulation in mTEC. In addition, p38 MAPK phosphorylation may require STAT6-dependent de novo protein synthesis induced by IL-13.

Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells. Publishing Authors By Initials

T Fujisawa,K Ide,MJ Holtzman,T Suda,K Suzuki,S Kuroishi,K Chida,H Nakamura,

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Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Respirology (Carlton, Vic.)

VOLUME: 13

Page Numbers: 191-202

Journal Abbreviation: Respirology

ISSN: 1323-7799

DAY: 14

MONTH: Mar

YEAR: 2008

Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells. Information

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LANGUAGE: eng

NlmUniqueID: 9616368

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Grant and Affiliation Information for Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in mouse tracheal epithelial cells.

AFFILIATION: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Country: Australia

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MEDLINETA: Respirology

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