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Inflammation Research

, Volume 47, Issue 8, pp 328–333 | Cite as

Ca2+-ATPase inhibitors and PKC activation synergistically stimulate TNF-α production in RBL-2H3 cells

  • R. Teshima
  • J. Onose
  • H. Ikebuchi
  • J. Sawada

Abstract.

Objective and Design: To investigate the effect of Ca2+-ATPase inhibitors on the production of TNF-α in rat basophilic leukemia (RBL-2H3) cells.¶Material: Two Ca2+-ATPase inhibitors, thapsigargin (TG) and cyclopiazonic acid (CPA), and three hydroquinone-antioxidants, 2,5-di-(tert-butyl)-1,4-hydroquinone (DTBHQ), 2,5-di-(tert/amyl)-1,4-hydroquinone (DTAHQ), 2-(tert-butyl)-1,4-hydroquinone (MTBHQ) were used.¶Treatment: Cells were treated with TG, CPA, DTBHQ, DTAHQ and MTBHQ for 3 h in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) and released TNF-α from the cells was measured (n >  or = 4).¶Results: All Ca2+-ATPase inhibitors (TG, CPA, DTBHQ and DTAHQ) induced TNF-α release in a dose-dependent manner. TNF-α release was inhibited by treatment with protein kinase C inhibitors (staurosporine, Ro31-8220, calophostin C) (p < or = 0.05). In contrast, MTBHQ, which does not induce increases in [Ca2+]i, did not induce the release of TNF-α. TNF-α release induced by DTBHQ and CPA was inhibited by treatment with actinomycin-D, the immunosuppressant FK506 and the glucocorticoid dexamethasone (p < or = 0.01).¶Conclusions: These results suggest 1) that [Ca2+]i increase and subsequent activation of protein kinase C is necessary for the release of TNF-α, and they work synergistically, 2) that the TNF-α release induced by Ca2+-ATPase inhibitors can be regulated at the transcriptional level.

Key words: Antioxidants — Ca2+-ATPase inhibitors — TNF-α— RBL-2H3 cells 

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Copyright information

© Birkhäuser Verlag, Basel, 1998

Authors and Affiliations

  • R. Teshima
    • 1
  • J. Onose
    • 2
  • H. Ikebuchi
    • 1
  • J. Sawada
    • 1
  1. 1.Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158, Japan, Fax +81 3 3707 6950, e-mail: rteshima@nihs.go.jpJP
  2. 2.Meiji College of Pharmacy, 1-35-23, Nozawa, Setagaya-ku, Tokyo 154, JapanJP

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