title: Platelet-activating factor modulates gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide.
abstract: Platelet-activating factor (PAF) is a phospholipid messenger implicated in mediation of inflammatory events associated with the resolution of inflammation. We applied the animal model of Helicobacter pylori LPS-induced gastritis in conjunction with prophylactic and therapeutic administration of a specific PAF antagonist, BN52020, to investigate the role of PAF in gastric mucosal responses to H. pylori infection. Prophylactic BN52020 administration produced up to 73.6% reduction in the severity of the LPS-induced inflammatory changes, whereas up to 38.4% increase in the severity of mucosal involvement occurred with BN52020 administered therapeutically. The prophylactic effects of BN52020 were accompanied by a drop in apoptosis and the expression of TNF-alpha and NOS-2, while BN52020 administered therapeutically caused a marked upregulation in apoptosis, TNF-alpha, and NOS-2. The untoward therapeutic effects of BN52020, moreover, were potentiated further in the presence of COX-2 inhibitor, whereas NOS-2 inhibitor caused a reduction in the extent of inflammatory changes. Our findings point to PAF as a key mediator of gastric mucosal inflammatory responses to H. pylori and suggest its modulatory role in the expression of COX-2 derived anti-inflammatory prostaglandins that are involved in controlling the extent of NOS-2 induction.
authors.affiliation: Research Center, Room C 875, University of Medicine and Dentistry of New Jersey, 110 Bergen Street, P.O. Box 1709, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: Bronislaw L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: Amalia
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2; D005753:Gastric Mucosa / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology*; D005756:Gastritis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D046934:Ginkgolides; D016481:Helicobacter Infections / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016480:Helicobacter pylori / Q000472:pathogenicity*; D018836:Inflammation Mediators / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D046934:Ginkgolides; D018836:Inflammation Mediators; D007527:Isoenzymes; D007783:Lactones; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; C442865:lipopolysaccharide, Helicobacter pylori; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C477042:ginkgolide A