Gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide: down-regulation of nitric oxide synthase-2 and caspase-3 by sulglycotide.
We applied the animal model of H. pylori lipopolysaccharide-induced gastritis to assess the effect of antiulcer agent, sulglycotide, on the mucosal inflammatory responses by analyzing the interplay between the activity of a key apoptotic caspase, caspase-3, epithelial cell apoptosis, and the expression of constitutive (cNOS) and inducible (NOS-2) nitric oxide synthase. H. pylori lipopolysaccharide applied intragastrically elicited within 4 days a pattern of mucosal responses resembling that of acute gastritis. This was accompanied by an 11.2-fold increase in epithelial cell apoptosis, a 6.5-fold induction in mucosal expression of NOS-2 and a 2.2-fold decline in cNOS, and a 5.4-fold increase in caspase-3 activity. Treatment with sulglycotide led to a 56.7% reduction in the extent of mucosal inflammatory changes elicited by H. pylori lipopolysaccharide and an 88.3% decrease in the epithelial cells apoptosis. Furthermore, this effect of sulglycotide was associated with a 51% decrease in mucosal expression of caspase-3 activity, a 73.7% decline in NOS-2, and a 64.1% increase in cNOS. The findings suggest that sulglycotide suppresses the H. pylori-induced mucosal inflammatory responses by up-regulating cNOS and interfering with the events propagated by NOS-2 and caspase-3.
Research Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, 07103-2400, USA.
B L
BL
Slomiany
J
J
Piotrowski
A
A
Slomiany
D000208:Acute Disease; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D005756:Gastritis / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016481:Helicobacter Infections / Q000201:enzymology* / Q000473:pathology; D016480:Helicobacter pylori; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
D000897:Anti-Ulcer Agents; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; C009354:sulglicotide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases