Activation of CD38 by interleukin-8 signaling regulates intracellular Ca2+ level and motility of lymphokine-activated killer cells
Activation of CD38 by interleukin-8 signaling regulates intracellular Ca2+ level and motility of lymphokine-activated killer cells
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DOI：
10.1074/jbc.m409592200
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发表时间：
2005-01-28
影响因子：
4.8
通讯作者：
Kim, UH
中科院分区：
文献类型：
--
作者：
Rah, SY;Park, KH;Kim, UH
CD38是一种adp -核糖基环化酶，产生一种有效的Ca2+动员剂环adp -核糖（cADPR）。在这项研究中，我们研究了CD38在淋巴因子激活的杀伤细胞（LAK）中的作用及其通过白细胞介素-8 （IL8）信号传导的调节。IAK细胞与IL8孵育后，细胞内cADPR水平升高，细胞内Ca2+浓度快速升高（[Ca2+](i)），并持续较长时间（bbb10 min）。拮抗cADPR类似物8-Br-cADPR（8-溴环腺苷二磷酸核糖）的预孵育，仅消除持续的Ca2+信号，但不消除初始的Ca2+升高。肌醇1,4,5-三磷酸（IP3）受体拮抗剂阻断了这两种Ca2+信号。有趣的是，在没有细胞外Ca2+的情况下，没有观察到持续的Ca2+升高。功能CD38-null (CD38(-)) LAK细胞在il - 8处理下表现出[Ca2+]的初始快速增加(i)，但没有持续的Ca2+升高。cGMP类似物8- pcpt -cGMP（8-（4-氯苯硫基）鸟苷-3′，5′-环单磷酸）可增加细胞cADPR水平，而cAMP类似物或phorbol 12-肉豆蔻酸13-醋酸酯未观察到cADPR水平升高。il - 8处理导致cGMP水平升高，而cGMP水平被IP3受体阻断剂抑制，而不被蛋白激酶C抑制剂抑制。cgmp介导的Ca2+升高被8-Br-cADPR阻断。此外，8-Br-cADPR和一种蛋白激酶G抑制剂可抑制il8介导的IAK细胞迁移。与这些观察结果一致，没有观察到il8诱导的CD38(-) IAK细胞的迁移。然而，直接应用cADPR或8-pCPT-cGMP刺激CD38细胞的迁移。这些结果表明，CD38受IL8受体的顺序激活、ip3介导的Ca2+升高和cGMP/蛋白激酶G的刺激，CD38在IL8诱导的LAK细胞迁移中起重要作用。
CD38 is an ADP-ribosyl cyclase, producing a potent Ca2+ mobilizer cyclic ADP-ribose (cADPR). In this study, we have investigated a role of CD38 and its regulation through interleukin-8 (IL8) signaling in lymphokine-activated killer (LAK) cells. Incubation of IAK cells with IL8 resulted in an increase of cellular cADPR level and a rapid rise of intracellular Ca2+ concentration ([Ca2+](i)), which was sustained for a long period of time (> 10 min). Preincubation of an antagonistic cADPR analog, 8-Br-cADPR (8-bromo-cyclic adenosine diphosphate ribose), abolished the sustained Ca2+ signal only but not the initial Ca2+ rise. An inositol 1,4,5-trisphosphate (IP3) receptor antagonist blocked both Ca2+ signals. Interestingly, the sustained Ca2+ rise was not observed in the absence of extracellular Ca2+. Functional CD38-null (CD38(-)) LAK cells showed the initial rapid increase of [Ca2+](i) but not the sustained Ca2+ rise in response to IL8 treatment. An increase of cellular cADPR level by cGMP analog, 8-pCPT-cGMP (8-(4-chlorophenylthio)guanosine-3',5'-cyclic monophosphate), but not cAMP analog or phorbol 12-myristate 13-acetate was observed. IL8 treatment resulted in the increase of cGMP level that was inhibited by the IP3 receptor blocker but not a protein kinase C inhibitor. cGMP-mediated Ca2+ rise was blocked by 8-Br-cADPR. In addition, IL8-mediated IAK cell migration was inhibited by 8-Br-cADPR and a protein kinase G inhibitor. Consistent with these observations, IL8-induced migration of CD38(-) IAK cells was not observed. However, direct application of cADPR or 8-pCPT-cGMP stimulated migration of CD38- cells. These results demonstrate that CD38 is stimulated by sequential activation of IL8 receptor, IP3-mediated Ca2+ rise, and cGMP/protein kinase G and that CD38 plays an essential role in IL8-induced migration of LAK cells.