Water extracts of Helicobacter pylori suppress the expression of histidine decarboxylase and reduce histamine content in the rat gastric mucosa.
BACKGROUND
Acute Helicobacter pylori (Hp) infection in humans may be associated with markedly reduced gastric acid secretion, but the mechanism of this hypochlorhydria has not been fully explained.


OBJECTIVE
This study was designed to investigate how water extracts (WE) of Hp applied on rat gastric mucosa affect gastric secretion and mucosal histamine concentration as well as the gene expression for histamine decarboxylase (HDC), the key enzyme converting histidine to histamine and for interleukin-1beta (IL-1beta), the important proinflammatory cytokine.


METHODS
Wistar rats were surgically equipped with small cannulas to form gastric fistulas (GF). Four weeks after formation of GF, rats received either saline (control group) or WE obtained from type I Hp strain expressing CagA/VacA proteins and from type II Hp strain negative for CagA/VacA. Hp-WE was applied intragastrically (i.g.) in a volume of 1 ml at days 0, 2, 4 and 6 (total 4 times). At days 7 and 14, the secretory tests were performed during which basal gastric acid and pepsin secretion was examined and acid and pepsin outputs were measured. After secretory tests, the rats were sacrificed, the stomachs removed and the damage to the gastric mucosa was assessed by measuring the lesion area planimetrically and by histology, the gene expression in gastric mucosa for HDC and interleukin-1beta (IL-1beta) was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot. Additionally, somatostatin concentration in gastric juice, gastric mucosal histamine content and plasma gastrin and IL-1beta levels were determined using radioimmunoassay (RIA).


RESULTS
Administration of Hp-WE failed to induce gross mucosal damage but microscopic examination revealed partial denudation of gastric surface epithelium without causing deep necrosis. In secretory tests, Hp-WE produced marked hypochlorhydria but type I Hp-WE induced significantly stronger inhibition of acid and pepsin secretion than type II Hp-WE, both at days 7 and 14. Both, type I and type II Hp-WE suppressed significantly the gene expression for HDC mRNA and lowered significantly gastric mucosal histamine content as compared to respective values in vehicle-treated control gastric mucosa. Furthermore, Hp-WE, resulted in a significant increase in expression of IL-1beta mRNA and a significant fall in luminal somatostatin concentration as well as a insignificant elevation of plasma gastrin level, the type I Hp-WE being more effective in these alterations than type II Hp-WE.


CONCLUSIONS
(1) Ability of Hp-WE to induce superficial damage, the reduction in HDC mRNA and accompanying fall in gastric histamine release, contribute, at least in part, to marked hypochlorhydria observed in the stomach exposed to repeated Hp-WE treatments, and (2) the deleterious effect of Hp-WE on the gastric mucosa involves an impairment of gastrin-somatostatin link possibly resulting from the action of Hp-derived toxins and the induction in mucosal cells of proinflammatory cytokine such as IL-1beta.
Konturek
P C
PC
Department of Medicine I, University Erlangen-Nuremberg, Erlangen, Germany.
Brzozowski
T
T
Karczewska
E
E
Duda
A
A
Bielański
W
W
Hahn
E G
EG
Konturek
S J
SJ
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000502:physiology*; D006632:Histamine / Q000032:analysis*; D006640:Histidine Decarboxylase / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology; D014867:Water
D005755:Gastrins; D007375:Interleukin-1; D014867:Water; D013004:Somatostatin; D006632:Histamine; D006640:Histidine Decarboxylase