The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts

Citation
Hj. Chae et al., The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts, BONE, 28(1), 2001, pp. 45-53
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","da verificare
Journal title
BONE
ISSN journal
8756-3282 → ACNP
Volume
28
Issue
1
Year of publication
2001
Pages
45 - 53
Database
ISI
SICI code
8756-3282(200101)28:1<45:TPMPKP>2.0.ZU;2-8
Abstract
The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tu mor necrosis factor-alpha), was studied in a human osteoblast cell line (MG -63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB transcription factor. When added to MG-63 cells, tumor necrosis facltor-alpha (TNF-alpha) had a stimulatory effect on the producti on of IL-6, and this elevation was significantly reduced by SB203580, a spe cific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release was also reduced by pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which has been reported to be a potent NF-kappaB inhibitor. Both the NF-kappaB i nhibitors in the presence of SB203580 had a more inhibitory effect on IL-6 release. In this study, TNF-alpha stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6, However, the specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha - induced NF-kappaB activation and both NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the TNF-alpha -stimulated osteoblasts. In addit ion, inhibition of p38 MAPK partially, but significantly, impaired TNF-alph a -regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kapp aB are required in TNF-alpha -induced IL-6 synthesis and that these two TNF -alpha -activated pathways can be primarily dissociated. Furthermore, p38 M APK may play a significant role in differentiation in MG-63 cells. (C) 2001 by Elsevier Science Inc. All rights reserved.