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Interleukin‐1β and tetradecanoylphorbol acetate‐induced biosynthesis of tumor necrosis factor α in human hepatoma cells involves the transcription factors ATF2 and c‐Jun and stress‐activated protein kinases
Author(s) -
Bauer Inge,
Al Sarraj Jude,
Vinson Charles,
Larsen Reinhard,
Thiel Gerald
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21075
Subject(s) - tumor necrosis factor alpha , 12 o tetradecanoylphorbol 13 acetate , proinflammatory cytokine , transcription factor , biology , microbiology and biotechnology , cytokine , cancer research , kinase , chemistry , protein kinase c , immunology , inflammation , biochemistry , gene , phorbol ester
The proinflammatory cytokine tumor necrosis factor (TNF) α is mainly produced in cells from the monocyte/macrophage lineage. TNFα is also a key signaling molecule in the liver functioning as an important physiological and pathogenic mediator. In hepatocytes or human hepatoma cells TNFα is expressed at extremely low levels but TNFα biosynthesis can be induced by interleukin (IL)‐1β or 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA). Here, we show that IL‐1β and TPA stimulated TNFα gene transcription in hepatoma cells mediated by a composite TPA‐responsive element/cAMP response element. Both IL‐1β and TPA triggered phosphorylation and activation of the basic region leucine zipper transcription factors c‐Jun and ATF2 and expression of dominant‐negative mutants of c‐Jun and ATF2‐reduced TNFα promoter activity and secretion of TNFα. Expression of the nuclear dual‐specific MAP kinase phosphatase‐1 (MKP‐1) blocked TNFα promoter activity and TNFα secretion following IL‐1β or TPA stimulation, indicating that MKP‐1 functions as a nuclear shut‐of‐device of IL‐1β and TPA‐induced TNFα expression. J. Cell. Biochem. 100: 242–255, 2007. © 2006 Wiley‐Liss, Inc.