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Differential regulation of tumour necrosis factor‐α mRNA degradation in macrophages by interleukin‐4 and interferon‐γ
Author(s) -
SUK K.,
ERICKSON K. L.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.500561.x
Subject(s) - lymphokine , tumor necrosis factor alpha , biology , cytokine , interferon , interleukin , microbiology and biotechnology , interferon gamma , lipopolysaccharide , immunology , immune system
Interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) have been reported previously to mediate similar as well as antagonistic effects on murine macrophage functions. One effect common to both is the enhancement of tumour necrosis factor‐α (TNF‐α) secretion in macrophages. To assess further the effects of these two lymphokines on macrophage TNF‐α production, we investigated the role of these lymphokines in the induction and stability of TNF‐α messages along with interleukin‐1 (IL‐1) as a comparison. IFN‐γ and IL‐4 increased lipopolysaccharide (LPS)‐induced TNF‐α, IL‐1 steady‐state message levels. In contrast to IL‐1 messages, whose degradation was not significantly affected by either lymphokine, the stability of TNF‐α messages differed after IFN‐γ and IL‐4 treatment. Although IL‐4 treatment increased the TNF‐α transcription rate, an increase in the degradation rate of TNF‐α mRNA in the IL‐4‐treated cells resulted in a lower level of steady‐state mRNA than in the IFN‐γ‐treated cells. Additionally, a 18 000 MW cytoplasmic factor was found to have specific binding activity to the AU‐rich sequences of the TNF‐α message in peritoneal macrophages. Although the binding activity of this factor was not affected by either IFN‐γ or IL‐4, the binding of the factor to AU‐rich sequences appeared to be important in the rapid degradation of TNF‐α messages. Thus IFN‐γ and IL‐4 may differentially affect the post‐transcriptional control of TNF‐α gene expression. And this lymphokine‐mediated post‐transcriptional control of the TNF‐α gene does not appear to involve the alteration of binding activity of the 18 000 MW AU‐rich sequence binding factor.

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