1997•Journal of Biological ChemistryOpen access

Interleukin-4 and -13 Inhibit Tumor Necrosis Factor-α mRNA Translational Activation in Lipopolysaccharide-induced Mouse Macrophages

Tatjana Mijatovic, Véronique Kruys, Daniel Caput, Patrick Defrance, Georges A. Huez

Abstract

The production of tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated macrophages can be markedly inhibited by the two closely related cytokines, interleukin (IL)-4 and IL-13. To investigate the molecular mechanism of this inhibition, we analyzed the effect of the two cytokines on TNF-alpha production and TNF-alpha mRNA accumulation in the mouse macrophage cell lines RAW 264.7 and J774 stimulated by LPS. Whereas LPS-induced TNF-alpha production is strongly suppressed by both cytokines, TNF-alpha mRNA accumulation is not significantly affected, indicating that IL-4 and IL-13 induce a translational repression of TNF-alpha mRNA. Transfection of reporter gene constructs containing different regions of the TNF-alpha gene revealed that the inhibitory action of IL-4 and IL-13 is mediated by the UA-rich sequence present in the TNF-alpha mRNA 3'-untranslated region.

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Key concepts: Tumor necrosis factor alpha, Lipopolysaccharide, Tumor necrosis factor α, Messenger RNA, Interleukin, Interleukin 1β, Cancer research, Interleukin 19