Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.
- Author:
Yunjeong JO
1
;
Sang Uk HAN
;
Yoon Jae KIM
;
Ju Hyeon KIM
;
Shin Tae KIM
;
Seong Jin KIM
;
Ki Baik HAHM
Author Information
1. Laboratory of Cell Regulation and Carcinogenesis, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea. hahmkb@hotmail.com
- Publication Type:Original Article
- Keywords:
Helicobacter pylori;
TGF-beta;
Inflammation;
Ulcer;
Host defense
- MeSH:
Blotting, Northern;
Enzyme-Linked Immunosorbent Assay;
Gastritis;
Helicobacter pylori;
Humans;
Inflammation;
Luciferases;
Oxidative Stress;
Transforming Growth Factor beta;
Transforming Growth Factor beta1;
Ulcer
- From:Gut and Liver
2010;4(1):43-53
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND/AIMS: Loss of transforming growth factor beta1 (TGF-beta1) 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-beta1 levels could be used to determine the outcome after H. pylori infection. METHODS: Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. RESULTS: The TGF-beta1 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-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. CONCLUSIONS: H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.
