Interleukin-8 production induced by the endozepine triakontatetraneuropeptide in human neutrophils: role of calcium and pharmacological investigation of signal transduction pathways.
The endozepine triakontatetraneuropeptide (TTN) induces intracellular calcium ([Ca(2+)](i)) changes and is chemotactic for human neutrophils (PMNs). Because interleukin-8 (IL-8) production is Ca(2+) dependent and can be induced by chemotactic stimuli, we have investigated the ability of TTN to induce IL-8 production in PMNs, as well as the signal transduction mechanisms involved. Our results show that TTN increases IL-8 release and IL-8 mRNA expression in a concentration- and time-dependent fashion, and these effects are prevented by the Ca(2+) chelator BAPTA-AM. TTN-induced [Ca(2+)](i) changes and IL-8 mRNA expression are sensitive to pertussis toxin, to the phospholipase C (PLC) inhibitor U73122 (but not to its inactive analogue U73343) and to the protein kinase C (PKC) inhibitor calphostin C. It is therefore suggested that TTN-induced IL-8 production in human PMNs results from a G protein-operated, PLC-activated [Ca(2+)](i) rise, and PKC contributes to this effect. These findings further support the possible role of TTN in the modulation of the inflammatory processes.
Marino
Franca
F
Laboratory of Pharmacology, Faculty of Medicine, University of Insubria, Via Ottorino Rossi n. 9, 21100 Varese, VA, Italy.
Cosentino
Marco
M
Fietta
Anna Maria
AM
Ferrari
Marco
M
Cattaneo
Simona
S
Frigo
Giuseppina
G
Lecchini
Sergio
S
Frigo
Gian Mario
GM
D002118:Calcium / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D009479:Neuropeptides / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D009479:Neuropeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C060941:triakontatetraneuropeptide; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium