Differential regulation of human B-lymphocyte tumor necrosis factor- alpha
(TNF-alpha) and lymphotoxin (TNF-beta) production by protein phosphatase 1
and 2A inhibitor
HZ Xia, CC Kannapell, SM Fu and SS Sung
Department of Internal Medicine, University of Virginia, Charlottesville.
Tumor necrosis factor (TNF) and lymphotoxin (LT; TNF-beta) are major
cytokines produced by B lymphocytes. Stimulation by okadaic acid, a
phosphatase 1 and 2A inhibitor, markedly increased TNF mRNA accumulation
and cytokine production. On the other hand, the accumulation of LT mRNA was
not affected by okadaic acid despite structural and functional similarities
between TNF and LT. The increase in TNF mRNA accumulation was due to the
stimulation of gene transcription and a marked stabilization of this mRNA.
The binding activities of the transcription factors AP-1 and AP-2 and NF
kappa B, which regulates TNF gene transcription, were also stimulated by
okadaic acid. In addition, okadaic acid was shown to increase TNF
production at the protein level. These results show the importance of
protein phosphatases in the regulation of cytokine production in B cells,
and further identifies differences in the regulation of TNF-alpha and LT
production.
Volume 82,
Issue 9,
pp. 2806-2812,
11/01/1993
Copyright © 1993 by The American Society of Hematology
