The protein kinase C activator Bryostatin-1 induces the rapid release of TNF alpha from MONO-MAC-6 cells.

Abstract:

:Bryostatin-1 is a natural activator of protein kinase C and currently examined in phase I trials as anticancer agent. We found that Bryostatin-1 induced tumor necrosis factor alpha (TNF alpha) expression in the human cell line MONO-MAC-6. Using Northern blot analysis and a bioassay for the detection of the cytokine we observed that Bryo alone was sufficient to transiently induce mRNA synthesis and the rapid release of TNF alpha into the culture medium. However, the combination of Bryo with lipopolysaccharide resulted in a strong synergistic increase of TNF alpha secretion. The biologic activity of the secreted TNF alpha was amenable to inhibition by anti-TNF alpha antibodies. Blockade of the lipopolysaccharide receptor CD14 or inhibition of protein kinase C implied that both, CD14 and protein kinase C, are involved individually in signal transduction pathways leading to TNF alpha secretion from MONO-MAC-6 cells. The results demonstrate that Bryostatin-1 is able to induce TNF alpha secretion in human monocytes via a protein kinase C-dependent and CD14-independent pathway and by a mechanism which is most likely based on a strong increase of the TNF alpha mRNA level.

authors

Steube KG,Drexler HG

doi

10.1006/bbrc.1995.2413

subject

Has Abstract

pub_date

1995-09-25 00:00:00

pages

1197-203

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(85)72413-8

journal_volume

214

pub_type

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