Chronic gastritis with expression of inducible nitric oxide synthase is associated with high expression of interleukin-6 and hypergastrinaemia.
OBJECTIVE
High levels of inducible nitric oxide synthase and nitrotyrosine in Helicobacter pylori-infected gastric mucosa may contribute to development of gastric cancer. We investigated the relation between expression of inducible nitric oxide synthase and proinflammatory cytokines in gastric mucosa and serum markers of gastritis.


METHODS
The study included 103 patients with H. pylori infection. We examined levels of interleukin-1beta, interleukin-6 and interleukin-8 by enzyme-linked immunosorbent assay and evaluated expression of inducible nitric oxide synthase and nitrotyrosine by immunohistochemical staining. Furthermore, we assessed serum levels of pepsinogens, gastrin, anti-parietal cell antibody, nitrite and nitrate, as markers of gastritis.


RESULTS
Thirty-seven of 103 (35.6%) gastric mucosa specimens showed simultaneous expression of inducible nitric oxide synthase and nitrotyrosine. In these patients (inducible nitric oxide synthase-positive group), the serum level of gastrin was significantly higher than that of the inducible nitric oxide synthase-negative group (509.5 +/- 141.5 pg/mL vs. 210.0 +/- 227.2 pg/mL; P < 0.01), whereas there were no significant differences in serum levels of pepsinogen, anti-parietal cell antibody, and nitrate and nitrite or in scores of histological gastritis. Interleukin-6 levels were significantly higher in the inducible nitric oxide synthase-positive group than in the inducible nitric oxide synthase-negative group (25.9 +/- 7.0 pg/mg protein vs. 10.6 +/- 4.9 pg/mg protein; P < 0.05).


CONCLUSIONS
Inducible nitric oxide synthase-producing gastritis was correlated with high levels of interleukin-6. Patients with hypergastrinaemia should be carefully followed on a long-term basis to ensure that the development of any malignancy is detected early.
Kai
H
H
Department of Medicine and Molecular Science, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
Ito
M
M
Kitadai
Y
Y
Tanaka
S
S
Haruma
K
K
Chayama
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000097:blood*; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D015415:Biomarkers; D005755:Gastrins; D015850:Interleukin-6; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II