Differential regulation of human B-lymphocyte tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin (TNF-beta) production by protein phosphatase 1 and 2A inhibitor.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Xia HZ,Kannapell CC,Fu SM,Sung SS

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

2806-12

issue

9

eissn

0006-4971

issn

1528-0020

journal_volume

82

pub_type

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