RRC ID 39922
Author Kondo A, Koshihara Y, Togari A.
Title Signal transduction system for interleukin-6 synthesis stimulated by lipopolysaccharide in human osteoblasts.
Journal J Interferon Cytokine Res
Abstract Lipopolysaccharide (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions, and one of the roles is as a powerful stimulator of bone resorption. LPS stimulated bone resorption via CD14 in mouse calvaria and was reported to function as a receptor for bacterial LPS complexed with serum proteins. Interleukin-6 (IL-6) is capable of stimulating the differentiation of osteoclasts from their hematopoietic precursors, and LPS elevates IL-6 synthesis in human osteoblastic cells. However, the signaling pathway of LPS-induced IL-6 synthesis in osteoblasts is unknown. In the present study, we could detect the existence of CD14 in human osteoblastic cells by RT-PCR analysis and show that LPS increased IL-6 mRNA and synthesis via CD14 in human osteoblastic cells. In human osteoblasts (SaM-1 cells) treated with 10 microg/ml LPS, increases in IL-6 mRNA and synthesis were inhibited by anti-CD14 antibody (MEM-18), PD98059 (an inhibitor of classic mitogen-activated protein kinase [MAPK]), or SB203580 (an inhibitor of p38 MAPK) but were not inhibited by H-89 (an inhibitor of protein kinase A [PKA]) and calphostin C (an inhibitor of protein kinase C [PKC]). Furthermore, LPS-induced IL-6 synthesis was inhibited by curcumin (an inhibitor of activating protein-1 [AP-1]) but not by pyrrolidine dithiocarbamate (PDTC) (an inhibitor of nuclear factor kappa B [NF-kappaB]). The findings of the present study suggest that the LPS receptor CD14, existent in human osteoblastic cells, and IL-6 synthesis in response to LPS probably occur via CD14, p38 MAPK, and MAP kinase/extracellular-regulated kinase kinase (MEK), leading to the transcriptional activation of AP-1 in human osteoblastic cells.
Volume 21(11)
Pages 943-50
Published 2001-11-1
DOI 10.1089/107999001753289550
PMID 11747626
MeSH Adult Cell Line Curcumin / pharmacology Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Enzyme Inhibitors / pharmacology Humans Interleukin-6 / biosynthesis* Interleukin-6 / genetics Kinetics Lipopolysaccharide Receptors / biosynthesis Lipopolysaccharide Receptors / genetics Lipopolysaccharides / pharmacology* MAP Kinase Signaling System* / drug effects Male Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinases / antagonists & inhibitors NF-kappa B / antagonists & inhibitors Osteoblasts / drug effects Osteoblasts / metabolism* Osteosarcoma Protein Kinase C / antagonists & inhibitors Pyrrolidines / pharmacology RNA, Messenger / biosynthesis Thiocarbamates / pharmacology Transcriptional Activation* Tumor Cells, Cultured p38 Mitogen-Activated Protein Kinases
IF 2.032
Times Cited 21
Human and Animal Cells Saos-2(RCB0428)