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 I...

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Bibliographic Details
Published in:Cellular signalling 2003-05, Vol.15 (5), p.511-517
Main Authors: Marino, Franca, Cosentino, Marco, Fietta, Anna Maria, Ferrari, Marco, Cattaneo, Simona, Frigo, Giuseppina, Lecchini, Sergio, Frigo, Gian Mario
Format: Article
Language:English
Subjects:
Calcium - physiology
Chelating Agents - pharmacology
Diazepam-binding inhibitor
Dose-Response Relationship, Drug
Egtazic Acid - analogs & derivatives
Egtazic Acid - pharmacology
Endozepines
Enzyme Inhibitors - pharmacology
Gene Expression Regulation
Humans
IL-8
IL-8 mRNA
Interleukin-8 - biosynthesis
Interleukin-8 - genetics
Intracellular calcium
Kinetics
Neuropeptides - pharmacology
Neutrophils - drug effects
Neutrophils - immunology
Peptide Fragments - pharmacology
Pertussis Toxin - pharmacology
Protein Kinase C - antagonists & inhibitors
RNA, Messenger - biosynthesis
Signal Transduction - drug effects
TTN
Type C Phospholipases - antagonists & inhibitors
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Summary: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.
ISSN:0898-6568
1873-3913
DOI:10.1016/S0898-6568(02)00134-1