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Article

HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK

  • Authors:
    • Kazuhiko Fujita
    • Takanobu Otsuka
    • Tetsu Kawabata
    • Shingo Kainuma
    • Go Sakai
    • Rie Matsushima‑Nishiwaki
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan
  • Pages: 2185-2192
    |
    Published online on: July 18, 2018
       https://doi.org/10.3892/ijmm.2018.3785
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Abstract

Heat shock protein 90 (HSP90), expressed abundantly in a variety of cell types, is a molecular chaperone, and has a central role in protein homeostasis under stress conditions. In our previous study, it was shown that thrombin stimulates interleukin‑6 (IL‑6) synthesis via p44/p42 mitogen‑activated protein kinase (MAPK) and p38 MAPK in osteoblast‑like MC3T3‑E1 cells, and that Rho‑kinase acts as a positive regulator at a point upstream of p38 MAPK, but not p44/p42 MAPK. The present study investigated whether or not HSP90 is involved in the thrombin‑stimulated synthesis of IL‑6 and examined the mechanism by which HSP90 is involved in MC3T3‑E1 cells. Cultured cells were stimulated by treatment with thrombin. IL‑6 concentrations in MC3T3‑E1 cells were determined using an ELISA assay, and levels of phosphorylated p38 MAPK, p44/p42 MAPK and myosin phosphatase targeting subunit, a substrate of Rho‑kinase; were analyzed by western blotting. The 17‑allylamino‑17demethoxy‑geldanamycin (17‑AAG) and 17‑dimethylamino‑ethylamino‑17‑demethoxy‑geldanamycin (17‑DMAG) HSP90 inhibitors significantly enhanced the thrombin‑stimulated release of IL‑6. Geldanamycin, another inhibitor of HSP90, also upregulated the release and mRNA expression of IL‑6. 17‑AAG and geldanamycin markedly potentiated the thrombin‑induced phosphorylation of p38 MAPK without affecting the phosphorylation of p44/p42 MAPK or myosin phosphatase targeting subunit, a substrate of Rho‑kinase. Additionally, the enhancement by 17‑AAG of the thrombin‑stimulated release of IL‑6 was significantly reduced by SB203580, an inhibitor of p38 MAPK. These results suggested that the thrombin‑stimulated synthesis of IL‑6 was limited by HSP90 in osteoblasts, and that the effects of HSP90 were exerted at the point between Rho‑kinase and p38 MAPK.
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Copy and paste a formatted citation
Spandidos Publications style
Fujita K, Otsuka T, Kawabata T, Kainuma S, Sakai G, Matsushima‑Nishiwaki R, Kozawa O and Tokuda H: HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK. Int J Mol Med 42: 2185-2192, 2018.
APA
Fujita, K., Otsuka, T., Kawabata, T., Kainuma, S., Sakai, G., Matsushima‑Nishiwaki, R. ... Tokuda, H. (2018). HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK. International Journal of Molecular Medicine, 42, 2185-2192. https://doi.org/10.3892/ijmm.2018.3785
MLA
Fujita, K., Otsuka, T., Kawabata, T., Kainuma, S., Sakai, G., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK". International Journal of Molecular Medicine 42.4 (2018): 2185-2192.
Chicago
Fujita, K., Otsuka, T., Kawabata, T., Kainuma, S., Sakai, G., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK". International Journal of Molecular Medicine 42, no. 4 (2018): 2185-2192. https://doi.org/10.3892/ijmm.2018.3785
Copy and paste a formatted citation
x
Spandidos Publications style
Fujita K, Otsuka T, Kawabata T, Kainuma S, Sakai G, Matsushima‑Nishiwaki R, Kozawa O and Tokuda H: HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK. Int J Mol Med 42: 2185-2192, 2018.
APA
Fujita, K., Otsuka, T., Kawabata, T., Kainuma, S., Sakai, G., Matsushima‑Nishiwaki, R. ... Tokuda, H. (2018). HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK. International Journal of Molecular Medicine, 42, 2185-2192. https://doi.org/10.3892/ijmm.2018.3785
MLA
Fujita, K., Otsuka, T., Kawabata, T., Kainuma, S., Sakai, G., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK". International Journal of Molecular Medicine 42.4 (2018): 2185-2192.
Chicago
Fujita, K., Otsuka, T., Kawabata, T., Kainuma, S., Sakai, G., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."HSP90 limits thrombin‑stimulated IL‑6 synthesis in osteoblast‑like MC3T3‑E1 cells: Regulation of p38 MAPK". International Journal of Molecular Medicine 42, no. 4 (2018): 2185-2192. https://doi.org/10.3892/ijmm.2018.3785
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