Suppression of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide by sulglycotide.
The effect of the antiulcer agent sulglycotide on gastric epithelial cell apoptosis and the expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) during Helicobacter pylori lipopolysaccharide-induced acute gastritis was investigated. Rats, pretreated twice daily for 3 consecutive days with sulglycotide at 200 mg/kg or vehicle, were subjected to surface epithelial application of H. pylori lipopolysaccharide (50 microg/animal), and, after 4 additional days on the drug or vehicle regimen, their mucosal tissue was used for histologic assessment, quantitation of TNF-alpha and IL-4, and the assay of epithelial cell apoptosis. In the absence of sulglycotide, H. pylori lipopolysaccharide caused acute mucosal responses manifested by the inflammatory infiltration of the lamina propria with lymphocytes and plasma cells, edema, hyperemia, and epithelial hemorrhage. These responses were accompanied by an 11-fold increase in epithelial cell apoptosis and a 9-fold enhancement of the mucosal expression of proinflammatory cytokine TNF-alpha. However, the mucosal expression of regulatory cytokine IL-4 decreased by 15%. Treatment with sulglycotide produced significant (56.6%) reduction in the extent of acute mucosal inflammatory changes caused by H. pylori lipopolysaccharide. Moreover, the effect of sulglycotide was manifested in an 88.3% reduction in the epithelial cell apoptosis and a 69.1% decrease in the mucosal expression of TNF-alpha, whereas the expression of IL-4 showed only marginal (6%) enhancement. The results suggest that the cytoprotective agent sulglycotide suppresses the inflammatory and apoptotic events elicited in gastric mucosa by H. pylori lipopolysaccharide through stimulation of TNF-alpha expression.
Slomiany
B L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA.
Piotrowski
J
J
Slomiany
A
A
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; C009354:sulglicotide