PROTEIN-KINASE A-DEPENDENT IL-6 PRODUCTION INDUCED BY CALCITONIN IN HUMAN GLIOBLASTOMA A172 CELLS

In human glioblastoma A172 cells, interleukin-6 (IL-6) production was induced by interleukin-1 beta (IL-1 beta) and dibutyryl cyclic AMP. Th ese cells have been shown to induce IL-6 production via a cAMP-protein kinase A system. Since calcitonin (CT) and calcitonin gene-related pe ptide (CGRP) are known to increase cAMP accumulation in murine and rat astrocytes, we examined whether these neuropeptides induced IL-6 prod uction in A172 cells. Human CT and human CGRP increased IL-6 productio n and cAMP accumulation in a dose-dependent manner. A specific protein kinase A inhibitor, H-89, inhibited both CT- and CGRP-induced IL-6 pr oduction. CT and CGRP have been shown to cross-react with each other. To exclude the possibility of this cross-reactivity, we studied the ad ditive effects of CT and CGRP and the inhibitory effects of specific i nhibitors. When 100 nM CT was added, cAMP accumulation stimulated by 1 0 nM CGRP (the maximal dose) was increased. CGRP (8-37), a specific CG RP receptor inhibitor, inhibited cAMP accumulation and IL-6 production induced by CGRP, but did not inhibit these effects when they were ind uced by CT. Salmon CT (8-32), a specific inhibitor of the CT receptor, inhibited cAMP accumulation induced by CT, but did not inhibit the ef fect 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.