Add time:07/20/2019         Source:sciencedirect.com

The endozepine triakontatetraneuropeptide (cas 120667-90-5) (TTN) induces intracellular calcium ([Ca2+]i) changes and is chemotactic for human neutrophils (PMNs). Because interleukin-8 (IL-8) production is Ca2+ 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 Ca2+ chelator BAPTA-AM. TTN-induced [Ca2+]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 [Ca2+]i rise, and PKC contributes to this effect. These findings further support the possible role of TTN in the modulation of the inflammatory processes.

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