scholarly journals Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, inhibits induction of acute-phase proteins by interleukin-6 alone or in combination with interleukin-1 in human hepatoma cell lines

1992 ◽  
Vol 286 (3) ◽  
pp. 983-983
1990 ◽  
Vol 269 (1) ◽  
pp. 41-46 ◽  
Author(s):  
M K Ganapathi ◽  
A Mackiewicz ◽  
D Samols ◽  
A Brabenec ◽  
I Kushner ◽  
...  

Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine. The induction observed in the presence of conditioned medium plus caffeine was as much as 180-fold, comparable with that seen after many stimuli in vivo. This potentiation was accompanied by an increase in the levels of CRP mRNA. By contrast, no potentiating effect on CRP induction by conditioned medium was found when we tested theophylline, forskolin, 8-bromo cyclic AMP or two Ca2+ ionophores, namely ionomycin and A23187. None of the above compounds, including caffeine, when tested alone, had any detectable effect on the synthesis and secretion of CRP. Our previous study [Ganapathi, May, Schultz, Brabenec, Weinstein, Sehgal & Kushner (1988) Biochem. Biophys. Res. Commun. 157, 271-277], employing defined cytokines, had shown that induction of CRP in Hep 3B cells requires IL(interleukin)-6 plus IL-1, whereas, in the NPLC/PRF/5 cell line, IL-6 alone is effective. Caffeine similarly potentiated induction of CRP by these defined cytokine signals in these two cell lines. Changes in synthesis of other acute-phase proteins, including serum amyloid A (SAA), alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin and albumin, induced by conditioned medium or, in some cases, by IL-6 and/or IL-1 alpha, were only minimally affected by caffeine. Thus these results indicate that the mechanism by which caffeine potentiates CRP induction by cytokines appears to be independent of increases in intracellular concentrations of the two second messengers, cyclic AMP and Ca2+; the precise nature of this mechanism is unclear at the present time. Our results also indicate that the intracellular mechanisms by which cytokines regulate synthesis of CRP may differ from those regulating synthesis of some other acute-phase proteins. The differential response of CRP and SAA to caffeine is of particular interest, since induction of both of these two major acute-phase proteins can be accomplished by identical extracellular signals.


1992 ◽  
Vol 284 (3) ◽  
pp. 645-648 ◽  
Author(s):  
M K Ganapathi

Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction of alpha 1-proteinase inhibitor (alpha 1-PI) by IL-6 plus IL-1 or IL-6 alone was not significantly affected by OA up to concentrations of 20 nM, above which concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of CRP, fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration (80 nM). These results suggest that the signal transduction mechanisms regulating induction of acute-phase proteins by IL-6, either alone or in combination with IL-1, are mediated by activation of protein phosphatases 1 and/or 2A.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160843 ◽  
Author(s):  
Nicole Lange ◽  
Armelle Tsamo Tontsa ◽  
Claudia Wegscheid ◽  
Pierre Mkounga ◽  
Augustin Ephrem Nkengfack ◽  
...  

1998 ◽  
Vol 114 ◽  
pp. A1309 ◽  
Author(s):  
M. Nakamura ◽  
H. Saito ◽  
H. Ebinuma ◽  
M. Takahashi ◽  
F. Kaneko ◽  
...  

2006 ◽  
Vol 963 (1) ◽  
pp. 53-58 ◽  
Author(s):  
M. CERVELLO ◽  
L. GIANNITRAPANI ◽  
M. ROSA ◽  
M. NOTARBARTOLO ◽  
N. D'ALESSANDRO ◽  
...  

1982 ◽  
Vol 30 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Daniela Simon ◽  
David P. Aden ◽  
Barbara B. Knowles

1990 ◽  
Vol 81 (3) ◽  
pp. 216-219 ◽  
Author(s):  
Nobuyuki Ito ◽  
Sumio Kawata ◽  
Shinji Tamura ◽  
Kenji Takaishi ◽  
Ryuzo Saitoh ◽  
...  

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