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The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts.
Bone. 2001 Jan; 28(1):45-53.BONE

Abstract

The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor 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 factor-alpha (TNF-alpha) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific 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 inhibitors 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 addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-alpha-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kappaB are required in TNF-alpha-induced IL-6 synthesis and that these two TNF-alpha-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells.

Authors+Show Affiliations

Department of Dental Pharmacology and Wonkwang Dental Research Institute, College of Pharmacy, Center of Oriental Medicinal Science, Wonkwang University, Chonbuk, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11165942

Citation

Chae, H J., et al. "The P38 Mitogen-activated Protein Kinase Pathway Regulates Interleukin-6 Synthesis in Response to Tumor Necrosis Factor in Osteoblasts." Bone, vol. 28, no. 1, 2001, pp. 45-53.
Chae HJ, Chae SW, Chin HY, et al. The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts. Bone. 2001;28(1):45-53.
Chae, H. J., Chae, S. W., Chin, H. Y., Bang, B. G., Cho, S. B., Han, K. S., Kim, S. C., Tae, K. C., Lee, K. H., Kim, D. E., Im, M. K., Lee, S. J., Chang, J. Y., Lee, Y. M., Kim, H. M., Kim, H. H., Lee, Z. H., & Kim, H. R. (2001). The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts. Bone, 28(1), 45-53.
Chae HJ, et al. The P38 Mitogen-activated Protein Kinase Pathway Regulates Interleukin-6 Synthesis in Response to Tumor Necrosis Factor in Osteoblasts. Bone. 2001;28(1):45-53. PubMed PMID: 11165942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts. AU - Chae,H J, AU - Chae,S W, AU - Chin,H Y, AU - Bang,B G, AU - Cho,S B, AU - Han,K S, AU - Kim,S C, AU - Tae,K C, AU - Lee,K H, AU - Kim,D E, AU - Im,M K, AU - Lee,S J, AU - Chang,J Y, AU - Lee,Y M, AU - Kim,H M, AU - Kim,H H, AU - Lee,Z H, AU - Kim,H R, PY - 2001/2/13/pubmed PY - 2001/6/8/medline PY - 2001/2/13/entrez SP - 45 EP - 53 JF - Bone JO - Bone VL - 28 IS - 1 N2 - The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor 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 factor-alpha (TNF-alpha) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific 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 inhibitors 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 addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-alpha-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-kappaB are required in TNF-alpha-induced IL-6 synthesis and that these two TNF-alpha-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/11165942/The_p38_mitogen_activated_protein_kinase_pathway_regulates_interleukin_6_synthesis_in_response_to_tumor_necrosis_factor_in_osteoblasts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(00)00413-0 DB - PRIME DP - Unbound Medicine ER -