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Mechanisms of differential regulation of interleukin‐6 mRNA accumulation by tumor necrosis factor alpha and lymphotoxin during monocytic differentiation
Author(s) -
Brach Marion A.,
Cicco Nicola A,
Riedel Detlev,
Hirano Toshio,
Kishimoto Tadamitsu,
Mertelsmann Roland H.,
Herrmann Friedhelm
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)81411-g
Subject(s) - lymphotoxin , lymphotoxin alpha , tumor necrosis factor alpha , lymphotoxin beta receptor , tumor necrosis factors , interleukin 19 , immunology , interleukin , differential (mechanical device) , alpha (finance) , microbiology and biotechnology , chemistry , biology , cancer research , cytokine , medicine , physics , interleukin 5 , construct validity , thermodynamics , nursing , patient satisfaction
In the present report we compare the capacity of two related cytokines, tumor necrosis factor (TNF) alpha and lymphotoxin (LT), to modulate mRNA levels of interleukin‐6 (IL‐6) in cells representing different stages of monocytic differentiation including the human leukemia cell lines HL 60, U 937, THP‐1, MonoMac 1 and peripheral blood monocytes. We show that the capacity of TNF alpha and LT to induce IL‐6 mRNA accumulation increases as monocytic differentiation proceeds with TNF alpha being more potent than LT, suggesting that alternate pathways may be used by differentiating cells to control expression of IL‐6. In contrast, in monocytes which constitutively synthesize IL‐6 transcripts, TNF alpha and LT treatment had opposite effects on levels of IL‐6 mRNA accumulation. In these cells TNF alpha enhanced steady state levels of IL‐6 transcripts due to mRNA stabilization, whereas LT shortened IL‐6 mRNA half‐life, most likely due to induction of a RNA destabilizer since LT‐mediated downregulation of levels of IL‐6 mRNA in monocytes could be prevented by inhibition of protein synthesis. Neither TNF alpha nor LT altered IL‐6 mRNA accumulation by interfering with preexisting transcription factors since both TNF alpha and LT required de novo protein synthesis to exert their effects.