Kiriyama Y, Murayama T, Tokumitsu Y, Nomura Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
J Neuroimmunol. 1997 Jun;76(1-2):139-44. doi: 10.1016/s0165-5728(97)00044-1.
In human glioblastoma A172 cells, interleukin-6 (IL-6) production was induced by interleukin-1 beta (IL-1 beta) and dibutyryl cyclic AMP. These cells have been shown to induce IL-6 production via a cAMP-protein kinase A system. Since calcitonin (CT) and calcitonin gene-related peptide (CGRP) are known to increase cAMP accumulation in murine and rat astrocytes, we examined whether these neuropeptides induced IL-6 production in A172 cells. Human CT and human CGRP increased IL-6 production and cAMP accumulation in a dose-dependent manner. A specific protein kinase A inhibitor, H-89, inhibited both CT- and CGRP-induced IL-6 production. CT and CGRP have been shown to cross-react with each other. To exclude the possibility of this cross-reactivity, we studied the additive effects of CT and CGRP and the inhibitory effects of specific inhibitors. When 100 nM CT was added, cAMP accumulation stimulated by 10 nM CGRP (the maximal dose) was increased. CGRP (8-37), a specific CGRP receptor inhibitor, inhibited cAMP accumulation and IL-6 production induced by CGRP, but did not inhibit these effects when they were induced by CT. Salmon CT (8-32), a specific inhibitor of the CT receptor, inhibited cAMP accumulation induced by CT, but did not inhibit the effect induced by CGRP. These results demonstrated that CT can induce IL-6 production via cAMP accumulation and the effects of CT are mediated via its own receptors.
在人胶质母细胞瘤A172细胞中，白细胞介素 - 1β（IL - 1β）和二丁酰环磷酸腺苷可诱导白细胞介素 - 6（IL - 6）的产生。这些细胞已被证明可通过环磷酸腺苷 - 蛋白激酶A系统诱导IL - 6的产生。由于已知降钙素（CT）和降钙素基因相关肽（CGRP）可增加小鼠和大鼠星形胶质细胞中环磷酸腺苷的积累，我们研究了这些神经肽是否能诱导A172细胞产生IL - 6。人CT和人CGRP以剂量依赖的方式增加IL - 6的产生和环磷酸腺苷的积累。一种特异性蛋白激酶A抑制剂H - 89可抑制CT和CGRP诱导的IL - 6产生。CT和CGRP已被证明可相互交叉反应。为排除这种交叉反应的可能性，我们研究了CT和CGRP的叠加效应以及特异性抑制剂的抑制作用。当加入100 nM CT时，由10 nM CGRP（最大剂量）刺激的环磷酸腺苷积累增加。CGRP（8 - 37），一种特异性CGRP受体抑制剂，可抑制CGRP诱导的环磷酸腺苷积累和IL - 6产生，但不能抑制CT诱导的这些效应。鲑鱼降钙素（8 - 32），一种CT受体的特异性抑制剂，可抑制CT诱导的环磷酸腺苷积累，但不能抑制CGRP诱导的效应。这些结果表明，CT可通过环磷酸腺苷积累诱导IL - 6产生，且CT的作用是通过其自身受体介导的。
