Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn

Interleukin-33 (IL-33) is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in...

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Published in:	PloS one 2016-04, Vol.11 (4), p.e0154234-e0154234
Main Authors:	Sei, Hiroo, Oshima, Tadayuki, Shan, Jing, Wu, Liping, Yamasaki, Takahisa, Okugawa, Takuya, Kondo, Takashi, Tomita, Toshihiko, Fukui, Hirokazu, Watari, Jiro, Miwa, Hiroto
Format:	Article
Language:	eng
Subjects:	Acids Adaptive immunity Adult Aged Antacids - therapeutic use Biology and Life Sciences Biopsy Case-Control Studies Cell Nucleus - immunology Cell Nucleus - metabolism Chemokine CCL2 - genetics Chemokine CCL2 - immunology Chemokine CCL5 - genetics Chemokine CCL5 - immunology Chemokines Chromatin Cytokines Development and progression Disease Endoscopy Epithelial cells Epithelial Cells - immunology Epithelial Cells - metabolism Esophageal Mucosa - immunology Esophageal Mucosa - metabolism Esophagitis Esophagus Esophagus - immunology Esophagus - metabolism Extracellular Space - immunology Extracellular Space - metabolism Gastroenterology Gastroesophageal reflux Gene expression Gene Expression Regulation Genetic aspects Genetic regulation Heart Heartburn Heartburn - diagnosis Heartburn - genetics Heartburn - immunology Heartburn - metabolism Humans Immunity Immunofluorescence Inflammation Inflammatory diseases Interleukin Interleukin 6 Interleukin 8 Interleukin-33 - genetics Interleukin-33 - immunology Interleukin-6 - genetics Interleukin-6 - immunology Interleukin-8 - genetics Interleukin-8 - immunology Interleukins Medicine and Health Sciences Middle Aged Monocyte chemoattractant protein 1 Mucosa Nuclei Nuclei (cytology) Patients Physiological aspects Polymerase chain reaction Proteins RANTES Tissues Values
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Summary:	Interleukin-33 (IL-33) is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in both innate and adaptive immunity. We recently showed that IL-33 in esophageal mucosa is upregulated in reflux esophagitis. However, IL-33 expression in patients with heartburn without mucosal injury and its relationship with intercellular space (ICS) have never been examined. We therefore examined the expression of cytokines and ICS in patients with heartburn. The expression of IL-33 in the middle and distal esophageal mucosa of patients with heartburn without mucosal break and control samples was examined using real-time RT-PCR and immunofluorescence. The mRNA expression of IL-6, IL-8, MCP-1, and RANTES, and ICS was also analyzed. IL-33 expression and the mean ICS were significantly increased in the mucosa of patients with heartburn compared to that of the control. IL-33 and ICS were not different between the patients who were taking a PPI and those who were not. The upregulated IL-33 expression in the heartburn group was located in the nuclei of the basal cell layer. Although IL-6, IL-8, MCP-1 and RANTES levels were not different between control and patients with heartburn samples, IL-33 mRNA levels were still significantly correlated with IL-6, IL-8, or MCP-1 mRNA levels. Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.
ISSN:	1932-6203 1932-6203