RRC ID 39921
Author Kondo A, Mogi M, Koshihara Y, Togari A.
Title Signal transduction system for interleukin-6 and interleukin-11 synthesis stimulated by epinephrine in human osteoblasts and human osteogenic sarcoma cells.
Journal Biochem Pharmacol
Abstract Epinephrine increased gene- and protein-expression of interleukin-6 (IL-6) and interleukin-11 (IL-11), which are capable of stimulating the development of osteoclasts from their hematopoietic precursors, in human osteoblast (SaM-1) and human osteosarcoma (SaOS-2, HOS, and MG-63) cell lines. An increase in IL-6 and IL-11 synthesis in response to epinephrine appeared to be a common feature in osteoblastic cells, but the magnitude of expression was different in these cell lines. In HOS cells treated with epinephrine, increases of IL-6 and IL-11 synthesis were inhibited by timolol (a beta-blocker), H-89 (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide; an inhibitor of protein kinase A (PKA)) and SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole; an inhibitor of p38 mitogen-activated protein kinase (MAPK)], but not by phentolamine (an alpha-blocker), calphostin C [an inhibitor of protein kinase C (PKC)], or PD98059 (2'-amino-3'-methoxyflavone; an inhibitor of classic MAPK), suggesting a common pathway mediated by beta-adrenergic receptors in the PKA and p38 systems involved in the signal transduction of IL-6 and IL-11. Furthermore, expression of both genes was inhibited by curcumin [an inhibitor of activating protein-1 (AP-1) activation], but not by pyrrolidine dithiocarbamate (PDTC) [an inhibitor of nuclear factor (NF)-kappaB]. The pharmacological study suggested that coinduction of the two genes in response to epinephrine occurred via activation of AP-1. The findings of the present study suggest that coinduction of IL-6 and IL-11 in response to epinephrine probably occurs via the PKA and p38 MAPK systems, leading to the transcriptional activation of AP-1 in human osteoblastic cells.
Volume 61(3)
Pages 319-26
Published 2001-2-1
DOI 10.1016/s0006-2952(00)00544-x
PII S0006-2952(00)00544-X
PMID 11172736
MeSH Adrenergic Agonists / pharmacology* Adrenergic alpha-Antagonists / pharmacology Adrenergic beta-Antagonists / pharmacology Antioxidants / pharmacology Curcumin / pharmacology Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Drug Interactions Enzyme Inhibitors / pharmacology Enzyme-Linked Immunosorbent Assay Epinephrine / pharmacology* Gene Expression / drug effects Humans Interleukin-11 / biosynthesis* Interleukin-6 / biosynthesis* Mitogen-Activated Protein Kinases / antagonists & inhibitors NF-kappa B / antagonists & inhibitors Osteoblasts / drug effects* Osteoblasts / metabolism Osteosarcoma / metabolism* Osteosarcoma / pathology Protein Kinase C / antagonists & inhibitors Pyrrolidines / pharmacology RNA, Messenger / biosynthesis RNA, Messenger / drug effects Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* / drug effects Thiocarbamates / pharmacology Transcription Factor AP-1 / antagonists & inhibitors Tumor Cells, Cultured
IF 4.96
Times Cited 55
Human and Animal Cells Saos-2(RCB0428)