PMID- 9754866
OWN - NLM
STAT- MEDLINE
DCOM- 19990524
LR  - 20191210
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 47
IP  - 8
DP  - 1998 Aug
TI  - Ca2+-ATPase inhibitors and PKC activation synergistically stimulate TNF-alpha 
      production in RBL-2H3 cells.
PG  - 328-33
AB  - OBJECTIVE AND DESIGN: To investigate the effect of Ca2+-ATPase inhibitors on the 
      production of TNF-alpha 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-(tertbutyl)-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-Otetradecanoylphorbol-13-acetate (TPA) and 
      released TNF-alpha from the cells was measured (n > or = 4). RESULTS: All 
      Ca2--ATPase inhibitors (TG, CPA, DTBHQ and DTAHQ) induced TNF-alpha release in a 
      dose-dependent manner. TNF-alpha 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-alpha. TNF-alpha 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-alpha, and they work synergistically, 2) that the TNF-alpha 
      release induced by Ca2+-ATPase inhibitors can be regulated at the transcriptional 
      level.
FAU - Teshima, R
AU  - Teshima R
AD  - Division of Biochemistry and Immunochemistry, National Institute of Health 
      Sciences, Tokyo, Japan. rteshima@nihs.go.jp
FAU - Onose, J
AU  - Onose J
FAU - Ikebuchi, H
AU  - Ikebuchi H
FAU - Sawada, J
AU  - Sawada J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroquinones)
RN  - 0 (Indoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - 26XK13B61B (2,5-di-tert-butylhydroquinone)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - C12674942B (2-tert-butylhydroquinone)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Animals
MH  - Calcium-Transporting ATPases/*antagonists & inhibitors
MH  - Dactinomycin/pharmacology
MH  - Dexamethasone/pharmacology
MH  - Enzyme Activation/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Hydroquinones/pharmacology
MH  - Indoles/pharmacology
MH  - Leukemia, Basophilic, Acute/*metabolism/pathology
MH  - Protein Kinase C/*metabolism/physiology
MH  - Rats
MH  - Tacrolimus/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/*drug effects
EDAT- 1998/10/01 00:00
MHDA- 1998/10/01 00:01
CRDT- 1998/10/01 00:00
PHST- 1998/10/01 00:00 [pubmed]
PHST- 1998/10/01 00:01 [medline]
PHST- 1998/10/01 00:00 [entrez]
AID - 10.1007/s000110050337 [doi]
PST - ppublish
SO  - Inflamm Res. 1998 Aug;47(8):328-33. doi: 10.1007/s000110050337.