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 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.
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Hiroo
H
Sei
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Tadayuki
T
Oshima
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.|Depertment of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, China.
Jing
J
Shan
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.|Depertment of Gastroenterology, The Third People's Hospital of Chengdu, Chengdu, China.
Liping
L
Wu
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Takahisa
T
Yamasaki
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Takuya
T
Okugawa
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Takashi
T
Kondo
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Toshihiko
T
Tomita
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Hirokazu
H
Fukui
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Jiro
J
Watari
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Hiroto
H
Miwa
D000328:Adult; D000368:Aged; D000863:Antacids / Q000627:therapeutic use; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D000071041:Esophageal Mucosa / Q000276:immunology / Q000378:metabolism*; D004947:Esophagus / Q000276:immunology / Q000378:metabolism*; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006356:Heartburn / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008875:Middle Aged
D000863:Antacids; C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; C506536:IL33 protein, human; C508600:IL6 protein, human; D000067596:Interleukin-33; D015850:Interleukin-6; D016209:Interleukin-8