Epidermal growth factor and transforming growth factor alpha in duodenal ulcer and non-ulcer dyspepsia patients before and after Helicobacter pylori eradication.
BACKGROUND
Epidermal growth (EGF) and transforming growth factor alpha (TGFalpha) are potent gastric secretory inhibitors, mitogens, and mucosal protectors, but the impact of Helicobacter pylori infection on their mucosal expression and luminal release has not been clarified.


METHODS
In this study, gene and immunoreactive and immunohistochemical expressions of EGF and TGFalpha were assessed in the gastric mucosa of 15 H. pylori-negative healthy normals, in 22 H. pylori-positive duodenal ulcer patients (DU) and in 24 H. pylori-positive non-ulcer dyspepsia patients (NUD). All studies in DU and NUD patients were repeated after 2 weeks of triple therapy (amoxicillin + clarithromycin + omeprazole) and 4 weeks and 2 years later.


RESULTS
Immunohistochemical expression of EGF and TGFalpha in H. pylori-positive DU and NUD was significantly higher than in H. pylori-negative normals, and this increase persisted at 2 and 4 weeks after therapy but normalized 2 years later. EGF mRNA was detected in the gastric mucosa of H. pylori-positive DU before and at 2 and 4 weeks after H. pylori eradication, but it was not found 2 years after the eradication of H. pylori or in gastric mucosa of H. pylori-negative control subjects. TGFalpha mRNA was detected in the gastric mucosa independently of H. pylori status, with the stronger expression observed in the gastric mucosa of H. pylori-positive DU and NUD before eradication than after this procedure. Plasma gastrin, which was significantly increased in H. pylori-positive DU, normalized already after 2 weeks of triple therapy. The eradication rate as determined by histology after triple therapy reached 86.3% in DU patients and 90.5% in NUD patients. Two years after the eradication the H. pylori reinfection rate was 4.5% among DU patients and 4.2% among NUD. Treatment of DU patients with triple therapy resulted in complete ulcer healing.


CONCLUSIONS
1) Chronic H. pylori infection and resulting antral gastritis are associated with increased plasma gastrin and increased mucosal cell proliferation, probably due to enhanced expression of EGF and TGFalpha, and 2) the H. pylori eradication results in a decrease in plasma gastrin, but the increase in gastric TGFalpha and EGF content is sustained, suggesting that they may be involved in ulcer healing.
Konturek
P C
PC
Dept. of Medicine I and Institute of Pathology, University of Erlangen-Nuremburg, Erlangen, Germany.
Bobrzynski
A
A
Konturek
S J
SJ
Bielanski
W
W
Faller
G
G
Kirchner
T
T
Hahn
E G
EG
D000328:Adult; D002455:Cell Division; D004381:Duodenal Ulcer / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004415:Dyspepsia / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011863:Radioimmunoassay; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D005755:Gastrins; D018809:Proliferating Cell Nuclear Antigen; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor