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.

Frontiers in the bioarchaeology of stress and disease: Cross‐disciplinary perspectives from pathophysiology, human biology, and epidemiology

“…Calcitonin gene-related peptide (CGRP) is a potent vasodilator released at inflammatory sites to inhibit various macrophage, dendritic cell, and lymphocyte functions and presumably allows for greater availability of the edematous protein substrate necessary for osteoblasts to produce bone (Gomes et al, 2005). CGRP functions in local and systemic acute inflammation appears to inhibit tumor necrosis factor alpha (TNF-a), but its role in new bone formation is unclear, since it simultaneously downregulates bone resorption FRONTIERS IN THE BIOARCHAEOLOGY OF STRESS AND DISEASE but is associated with upregulation of sclerostin in a negative feedback loop (and see Kiriyama et al, 2001;Sasaki et al, 2000).…”

The Adenosine A2b Receptor: Its Role in Inflammation

“…Folliculostellate cells also express A1 receptors, which in contrast to A2 receptors, are negatively coupled to adenylate cyclase; such a scenario suggests a reciprocal control and fine tuning of the adenosine-signaling pathway that is dependent on the local level of adenosine [110]. How IL-6 acts as an anti-inflammatory molecule is unclear; in the pituitary gland it regulates, either directly or indirectly with other proinflammatory mediators, to secrete anti-inflammatory hormones including growth hormone, prolactin and ACTH [115][116][117][118][119]. IL-6 also stimulates adrenal steroidogenesis [120] and folliculostellate cells, like corticotrophs and somatotrophs also possess glucocorticoid receptors, suggesting their involvement in regulating stress and inflammation [121].…”

Calcitonin inhibits intervertebral disc degeneration by regulating protein kinase C

“…PKC is critical for the regulation of MAPK and Wnt pathways. We found that calcitonin also regulates the PKC signalling pathway 40 . Considering the critical role of PKC in matrix production in intervertebral disc, we studied the relationship between calcitonin and PKC pathway.…”

“…We found that calcitonin also regulates the PKC signalling pathway. 40 Considering the critical role of PKC in matrix production in intervertebral disc, we studied the relationship between calcitonin and PKC pathway. Our results showed that calcitonin can activate PKC-ε and inhibit PKC-δ, thereby exerting its protective role for IVDD.…”