Marino Franca, Cosentino Marco, Fietta Anna Maria, Ferrari Marco, Cattaneo Simona, Frigo Giuseppina, Lecchini Sergio, Frigo Gian Mario
Laboratory of Pharmacology, Faculty of Medicine, University of Insubria, Via Ottorino Rossi n. 9, 21100 Varese, VA, Italy.
Cell Signal. 2003 May;15(5):511-7. doi: 10.1016/s0898-6568(02)00134-1.
The endozepine triakontatetraneuropeptide (TTN) induces intracellular calcium (Ca(2+)) 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+) 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+) rise, and PKC contributes to this effect. These findings further support the possible role of TTN in the modulation of the inflammatory processes.
内源性阿片样肽三十烷四肽（TTN）可诱导细胞内钙（[Ca(2+)]i）变化，并且对人中性粒细胞（PMN）具有趋化作用。由于白细胞介素-8（IL-8）的产生依赖于Ca(2+)，且可由趋化刺激诱导，我们研究了TTN诱导PMN产生IL-8的能力以及相关的信号转导机制。我们的结果表明，TTN以浓度和时间依赖性方式增加IL-8释放和IL-8 mRNA表达，并且这些效应可被Ca(2+)螯合剂BAPTA-AM阻断。TTN诱导的[Ca(2+)]i变化和IL-8 mRNA表达对百日咳毒素、磷脂酶C（PLC）抑制剂U73122（但对其无活性类似物U73343不敏感）以及蛋白激酶C（PKC）抑制剂钙泊三醇C敏感。因此表明，TTN诱导人PMN产生IL-8是由G蛋白介导、PLC激活的[Ca(2+)]i升高所致，PKC也参与了这一效应。这些发现进一步支持了TTN在调节炎症过程中可能发挥的作用。
