title: Calcitonin induces IL-6 production via both PKA and PKC pathways in the pituitary folliculo-stellate cell line.
abstract: It has been demonstrated that calcitonin-binding sites are present in a variety of tissue types, including in the pituitary gland. Interleukin-6 (IL-6) is also produced in the pituitary and it regulates the secretion of various hormones. In this study, we examined the expression of the calcitonin receptor and the mechanism of IL-6 production induced by calcitonin in the pituitary folliculo-stellate cell line (TtT/GF). The mRNA of calcitonin receptor subtype C1a, but not that of C1b, was detected by RT-PCR in TtT/GF cells and in the normal mouse pituitary. Calcitonin increased cAMP accumulation and IL-6 production in a concentration-dependent manner in TtT/GF cells. As calcitonin activates the PKA and PKC pathways, we investigated the contributions of PKA and PKC to IL-6 production. IL-6 production was only slightly increased by either 8-bromo-cAMP (1 mM) or phorbol 12-myristate 13-acetate (100 nM) alone. However, IL-6 was synergistically induced in the presence of both 8-bromo-cAMP (1 mM) and phorbol 12myristate 13-acetate (100 nM). Furthermore, calcitonin-induced IL-6 production was completely suppressed by H-89 (PKA inhibitor) or GF109203X (PKC inhibitor), indicating that the activation of both PKA and PKC is necessary for calcitonin-induced IL-6 production. On the other hand, pertussis toxin (G(i)/G(o) signaling inhibitor) treatment achieved an approximately 9-fold increase in calcitonin-induced IL-6 production. These results show that calcitonin-stimulated IL-6 production is mediated via both PKA- and PKC-signaling pathways, whereas calcitonin also suppresses IL-6 production by activating G(i)/G(o) proteins in folliculo-stellate cells.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kiriyama
authors.forename: H
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: Y
authors.initials: Y
authors.lastname: Tokumitsu
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018003:Receptors, Calcitonin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D002116:Calcitonin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D015850:Interleukin-6; D011493:Protein Kinase C; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D000093242:Interleukin-6 Inhibitors