Related Experiment Video
Updated: Mar 22, 2026
Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
Published on: May 10, 2024
Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn
Hiroo Sei1, Tadayuki Oshima1, Jing Shan1,2
1Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.
Related Concept Videos
01:29Gastroesophageal Reflux Disease I: Meaning and Pathophysiology
01:29Gastroesophageal Reflux Disease II: Clinical Features and Management
Clinical Manifestations
GERD presents itself in a multitude of ways, with symptoms varying from person to person. The hallmark symptoms are...
01:22Pathophysiology of Peptic Ulcer Disease: Injurious Factors
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
01:21Barrett Esophagus-II: Clinical Manifestations and Management
To diagnose Barrett's esophagus, healthcare providers often recommend an endoscopy for those showing symptoms of acid reflux. The procedure...
01:30Peptic Ulcer Disease I: Introduction
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
01:30Esophageal Strictures-I: Introduction
Etiology
The primary cause of esophageal strictures is long-standing gastroesophageal reflux disease (GERD), accounting for about 70 to 80% of adult cases. Chronic acid reflux can lead to injury and scarring of the esophageal lining, culminating in...