An anti-inflammatory protein secreted from the rat seminal vesicle epithelium inhibits the synthesis of platelet-activating factor and the release of arachidonic acid and prostacyclin.
Platelet-activating factor (PAF), a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a mediator of inflammation and endotoxic shock produced by a variety of stimulated cells. Since the main biosynthetic pathway of PAF involves acetylation of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) generated from 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine by phospholipase A2, we suggest a general physiological role played by steroid-induced anti-(phospholipase A2) proteins in the modulation of PAF synthesis. The results of the present study support this hypothesis since an androgen-induced anti-inflammatory protein, SV-IV, secreted from rat seminal vesicles, inhibits PAF synthesis in stimulated polymorphonuclear neutrophils, macrophages and endothelial cells. SV-IV impairs PAF synthesis by inhibiting the activation of phospholipase A2, that also results in the inhibition of arachidonic acid and prostacyclin release, and of acetyl-CoA:lyso-PAF acetyltransferase.
Camussi
G
G
Dipartimento di Biochimica e Biofisica, Universitá di Napoli, Italy.
Tetta
C
C
Bussolino
F
F
Metafora
S
S
Peluso
G
G
Esposito
C
C
Porta
R
R
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000097:blood*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000097:blood*; D011464:Epoprostenol / Q000097:blood*; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D012669:Seminal Vesicles / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011464:Epoprostenol; D000123:Acetyltransferases; D013917:Thrombin