Epithelial-derived nuclear IL-33 aggravates inflammation in the pathogenesis of reflux esophagitis
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- 作者：Jing Shan ; Tadayuki Oshima ; Taichiro Muto ; Koubun Yasuda…
- 关键词：IL ; 33 ; Reflux esophagitis ; Inflammation ; Epithelial cell
- 刊名：Journal of Gastroenterology
- 出版年：2015
- 出版时间：April 2015
- 年：2015
- 卷：50
- 期：4
- 页码：414-423
- 全文大小：3,900 KB
- 参考文献：1. Souza, RF, Huo, X, Mittal, V (2009) Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology 137: pp. 1776-1784 CrossRef
2. Rieder, F, Biancani, P, Harnett, K (2010) Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis. Am J Physiol Gastrointest Liver Physiol 298: pp. G571-G581 CrossRef
3. Shan, J, Oshima, T, Chen, X (2012) Trypsin impaired epithelial barrier function and induced IL-8 secretion through basolateral PAR-2: a lesson from a stratified squamous epithelial model. Am J Physiol Gastrointest Liver Physiol 303: pp. G1105-G1112 CrossRef
4. Shan, J, Oshima, T, Fukui, H (2013) Acidic deoxycholic acid and chenodeoxycholic acid induce interleukin-8 production through p38 mitogen-activated protein kinase and protein kinase A in a squamous epithelial model. J Gastroenterol Hepatol 28: pp. 823-828 CrossRef
5. Ma, J, Altomare, A, Guarino, M (2012) HCl-induced and ATP-dependent upregulation of TRPV1 receptor expression and cytokine production by human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol 303: pp. G635-G645 CrossRef
6. Schmitz, J, Owyang, A, Oldham, E (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23: pp. 479-490 CrossRef
7. Meephansan, J, Tsuda, H, Komine, M (2012) Regulation of IL-33 expression by IFN-γ and tumor necrosis factor-α in normal human epidermal keratinocytes. J Invest Dermatol. 132: pp. 2593-2600 CrossRef
8. Lin, J, Zhang, L, Zhao, G (2013) A novel interleukin 33/ST2 signaling regulates inflammatory response in human corneal epithelium. PLoS One 8: pp. e60963 CrossRef
9. Carriere, V, Roussel, L, Ortega, N (2007) IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci USA 104: pp. 282-287 CrossRef
10. Ali, S, Mohs, A, Thomas, M (2011) The dual function cytokine IL-33 interacts with the transcription factor NF-κB to dampen NF-κB-stimulated gene transcription. J Immunol. 187: pp. 1609-1616 CrossRef
11. Pastorelli, L, Garg, RR, Hoang, SB (2010) Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci USA 107: pp. 8017-8022 CrossRef
12. Kobori, A, Yagi, Y, Imaeda, H (2010) Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol 45: pp. 999-1007 CrossRef
13. Chen, X, Oshima, T, Tomita, T (2011) Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins. Am J Physiol Gastrointest Liver Physiol 301: pp. G203-G209 CrossRef
14. Sakashita, M, Yoshimoto, T, Hirota, T (2008) Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis. Clin Exp Allergy 38: pp. 1875-1881 CrossRef
15. Oshima, T, Gedda, K, Koseki, J (2011) Establishment of esophageal-like non-keratinized stratified epithelium using normal human bronchial epithelial cells. Am J Physiol Cell Physiol 300: pp. C1422-C142 - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Gastroenterology
Oncology
Surgical Oncology
Hepatology
Internal Medicine
Colorectal Surgery - 出版者：Springer Japan
- ISSN：1435-5922
文摘
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 IL-33 was significantly upregulated in RE patients, and was located in the nuclei of basal and suprabasal layers. Upregulated IL-33 messenger RNA expression was correlated with IL-8 and IL-6 expression. In vitro, IL-33 was upregulated in the nuclei of basal and suprabasal layers by interferon-γ (IFNγ), and the upregulation was aggravated by the combination of deoxycholic acid (DCA) and IFNγ. IL-33 knockdown dampened IFNγ- and DCA-induced IL-8 and IL-6 production. IFNγ-induced IL-33 was inhibited by a Janus kinase inhibitor, a p38 mitogen-activated protein kinase inhibitor, and STAT1 siRNA. 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.