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Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase
Open accessAbstract
Involvement of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-6 gene expression of human fibroblast-like synoviocytes (FLSs) was assessed. p38 MAP kinase was constitutively expressed in human FLSs and activated in response to IL-1beta. A pyridinylimidazole compound, SB203580, inhibited p38 MAP kinase activity in vivo, since the activity of MAPKAP kinase-2 (a substrate of p38 MAP kinase) in IL-1beta-stimulated FLSs was totally suppressed by it. SB203580 concentration-dependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of SB203580 was dependent on de novo protein synthesis. SB203580 significantly reduced the stability of IL-6 mRNA without affecting the rate of IL-6 gene transcription. Here, we provide evidence that p38 MAP kinase is activated in response to IL-1beta in human FLSs and is involved in IL-6 synthesis by stabilizing IL-6 mRNA.
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Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T., Kashiwamura, S.-I., Nakajima, K., Koyama, K., Iwamatsu, A., et al. (1986) · Nature · doi:10.1038/324073a0 · Cited by 2,139
AU-rich elements: characterization and importance in mRNA degradation
Chen, C.-Y. A., & Shyu, A.-B. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89102-1 · Cited by 1,948
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768
Miyazawa, K., Mori, A., Yamamoto, K., & Okudaira, H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7620 · Cited by 69
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Wajant, H., Pfizenmaier, K., & Scheurich, P. (2003) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401189 · Cited by 2,359
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Chen, Z., Gibson, T. B., Robinson, F., Silvestro, L., Pearson, G., Xu, B.-E., Wright, A., Vanderbilt, C., & Cobb, M. H. (2001) · Chemical Reviews · doi:10.1021/cr000241p · Cited by 788
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Wang, W., Chen, J. X., Liao, R., Deng, Q., Zhou, J. J., Huang, S., & Sun, P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.10.3389-3403.2002 · Cited by 376
Metadata
- Authors
- Miyazawa, K., Mori, A., Miyata, H., Akahane, M., Ajisawa, Y., & Okudaira, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 273
- Issue
- 38
- Pages
- 24832-24838
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1981124481
- Cited by
- 224
- References
- 4
- FWCI
- 13.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Miyazawa, K., Mori, A., Miyata, H., Akahane, M., Ajisawa, Y., & Okudaira, H. (1998). Regulation of Interleukin-1β-induced Interleukin-6 Gene Expression in Human Fibroblast-like Synoviocytes by p38 Mitogen-activated Protein Kinase. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.38.24832
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