Abstract | BACKGROUND:
IL-33 is a new tissue-derived cytokine constitutively expressed in epithelial cells and plays a role in sensing damage caused by inflammatory diseases. The function of IL-33 in the esophageal mucosa has not been previously described. Accordingly, we examined the expression of IL-33 and its role in the pathogenesis of reflux esophagitis (RE). METHODS:
IL-33 in the esophageal mucosa of RE patients and in an in vitro stratified normal esophageal squamous epithelial model was examined at the messenger RNA and protein levels. The correlation of the level of IL-33 and IL-8 or IL-6 was examined. Cell layers were stimulated with bile acids and cytokines. IL-33 was knocked down by small interfering RNA ( siRNA). Pharmacological inhibitors and signal transducer and activator of transcription 1 (STAT1) siRNA were used. RESULTS: CONCLUSIONS: Nuclear IL-33 is upregulated in erosive mucosa of RE patients and is correlated with IL-8 and IL-6 levels. The normal esophageal epithelial model enables us to show for the first time that epithelial-cell-derived nuclear but not exogenous IL-33 is located upstream of the production of inflammatory cytokines and can aggravate the inflammation.
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Authors | Jing Shan, Tadayuki Oshima, Taichiro Muto, Koubun Yasuda, Hirokazu Fukui, Jiro Watari, Kenji Nakanishi, Hiroto Miwa |
Journal | Journal of gastroenterology
(J Gastroenterol)
Vol. 50
Issue 4
Pg. 414-23
(Apr 2015)
ISSN: 1435-5922 [Electronic] Japan |
PMID | 25129514
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- Interleukin-33
- Interleukins
- RNA, Messenger
- RNA, Small Interfering
- Interferon-gamma
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Topics |
- Case-Control Studies
- Cell Nucleus
(immunology)
- Cells, Cultured
- Epithelial Cells
(immunology)
- Esophagitis, Peptic
(immunology)
- Female
- Gene Expression Regulation
(immunology)
- Gene Knockdown Techniques
- Humans
- Immunity, Mucosal
- Inflammation Mediators
(metabolism)
- Interferon-gamma
(immunology)
- Interleukin-33
(biosynthesis, genetics, immunology)
- Interleukins
(biosynthesis)
- Male
- Mucous Membrane
(immunology)
- RNA, Messenger
(genetics)
- RNA, Small Interfering
(genetics)
- Signal Transduction
(immunology)
- Up-Regulation
(immunology)
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