Platelet activating factor stimulates arachidonic acid release in differentiated keratinocytes via arachidonyl non-selective phospholipase A2.
Platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is known to be present in excess in psoriatic skin, but its exact role is uncertain. In the present study we demonstrate for the first time the role of group VI PLA(2) in PAF-induced arachidonic acid release in highly differentiated human keratinocytes. The group IValpha PLA(2) also participates in the release, while secretory PLA(2)s play a minor role. Two anti-inflammatory synthetic fatty acids, tetradecylthioacetic acid and tetradecylselenoacetic acid, are shown to interfere with signalling events upstream of group IValpha PLA(2) activation. In summary, our major novel finding is the involvement of the arachidonyl non-selective group VI PLA(2) in PAF-induced inflammatory responses.
Jørgensen
Katarina Mariann
KM
Department of Biology, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Felberg
Hanne Solvang
HS
Berge
Rolf K
RK
Laegreid
Astrid
A
Johansen
Berit
B
D016718:Arachidonic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D054522:Group VI Phospholipases A2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D018836:Inflammation Mediators / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007527:Isoenzymes; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D009942:Organometallic Compounds / Q000378:metabolism; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000378:metabolism
D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D007476:Ionophores; D007527:Isoenzymes; D009942:Organometallic Compounds; D064801:Phospholipase A2 Inhibitors; D010972:Platelet Activating Factor; D013440:Sulfides; C410666:tetradecylselenoacetic acid; D016718:Arachidonic Acid; C037145:1-hexadecyl-2-acetyl-glycero-3-phosphocholine; C062078:1-(carboxymethylthio)tetradecane; D054513:Group IV Phospholipases A2; D054522:Group VI Phospholipases A2; C516389:PLA2G4A protein, human; C516475:PLA2G6 protein, human; D054467:Phospholipases A2; D054497:Phospholipases A2, Secretory; D002118:Calcium