Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response
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Background/Aims: Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation,oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1levels could be used to determine the outcome after H. pylori infection. Methods: Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results: The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression,whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16cells recovered to normal after 24 hr of H. pylori infection,but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions: H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr,but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.
Abstract
Background/Aims: Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation,oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1levels could be used to determine the outcome after H. pylori infection. Methods: Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results: The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression,whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16cells recovered to normal after 24 hr of H. pylori infection,but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions: H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr,but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.
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