Abstract
Interleukin (IL)-induced inflammatory responses are critical for the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. IL-33 represents a recently discovered proinflammatory cytokine involved in inflammatory diseases, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric IL-33 mRNA and protein expression were elevated in gastric mucosa of both patients and mice infected with H. pylori, which is positively correlated with bacterial load and the degree of gastritis. IL-33 production was promoted via extracellular regulated protein kinases (ERK) signaling pathway activation by gastric epithelial cells in a cagA-dependent manner during H. pylori infection, and resulted in increased inflammation and bacteria burden within the gastric mucosa. Gastric epithelial cell-derived IL-33 promoted TNF-α production from mast cells in vitro, and IL-33 increased TNF-α production in vivo. Increased TNF-α inhibited gastric epithelial cell proliferation, conducing to the progress of H. pylori-associated gastritis and bacteria colonization. This study defined a patent regulatory networks involving H. pylori, gastric epithelial cell, IL-33, mast cell, and TNF-α, which jointly play a pathological effect within the gastric circumstances. It may be a valuable strategy to restrain this IL-33-dependent pathway in the treatment of H. pylori-associated gastritis.
Highlights
Helicobacter pylori (H. pylori) is a Gram-negative bacteria, which has infected more than half of the world’s population
-uninfected gastric mucosa to evaluate the potential role of IL33 in H. pylori-associated immunopathogenesis, and found that, compared with uninfected donors, the levels of IL-33 mRNA (Fig. 1a) and protein (Fig. 1b) in gastric mucosa of H. pylori-infected patients were significantly higher, a result that was supported by immunofluorescence staining (Fig. 1c)
We found a positive correlation between IL-33 and H. pylori colonization (Fig. 1d), suggesting that H. pylori infection could induce the increase of IL-33
Summary
Helicobacter pylori (H. pylori) is a Gram-negative bacteria, which has infected more than half of the world’s population. Colonization and long-term infection of H. pylori in the human stomach almost always leads to chronic gastritis, even peptic ulceration or gastric tumor[1]. Inflammatory reaction to H. pylori infection shows special characteristics rarely seen in other organs or biological systems. Mast cells have been known for their notable role in anaphylaxis, they play a part in innate immune reactions against bacterial infection by secreting cellular factors[5]. Infiltration of mast cells is limited to a certain extent in normal mucosa. It is often elevated during inflammation[6]. A few studies have found that mast cells participated in chronic gastritis and they increased in number as the disease worsened[7]
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