Biphasic role of platelet-activating factor in oral mucosal ulcer healing.
Platelet-activating factor (PAF) is a potent phospholipid-derived messenger molecule involved in a number of pathological conditions, including mediation of inflammatory cascades associated with wound healing. We investigated prophylactic and therapeutic effects of a specific PAF antagonist, BN52020, on the course of experimentally induced oral mucosal ulcer healing. The prophylactic BN52020 administration produced an accelerated ulcer healing that was characterized by a marked induction in COX-2 enzyme protein expression and the substantial decline in apoptosis, TNF-alpha, and NOS-2 activity. A delay in ulcer healing, however, occurred with the therapeutic BN52020 administration, and this effect of the agent was reflected in a decreased expression of COX-2 protein, higher rate of apoptosis, and the elevated level of TNF-alpha and NOS-2. Our findings implicate PAF requirement in orderly progression of the events involved in oral tissue repair, and suggest that the interference with its actions during healing process results in the suppression of COX-2-derived anti-inflammatory prostaglandins that delay the mucosal repair.
Slomiany
Bronislaw L
BL
Research Center, University of Medicine and Dentistry of New Jersey, NJ Dental School, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
Slomiany
Amalia
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D018450:Disease Progression; D046934:Ginkgolides; D007527:Isoenzymes / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010972:Platelet Activating Factor / Q000737:chemistry / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014456:Ulcer / Q000378:metabolism* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D046934:Ginkgolides; D007527:Isoenzymes; D007783:Lactones; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C477042:ginkgolide A