Synergistic effect of ubiquitin on lipopolysaccharide-induced TNF-alpha production in murine macrophage cell line RAW 264.7 cells

Ubiquitin synergistically augmented the production of tumor necrosis factor alpha (TNF-alpha) in the presence of lipopolysaccharide (LPS) in murine ma crophage cell line RAW 264.7. To investigate the mechanism of this augmenta tion, we analyzed the effect of ubiquitin during TNF-alpha mRNA synthesis a nd degradation, and TNF-alpha degradation on RAW 264.7 cells stimulated by LPS. It is found that ubiquitin augmented TNF-alpha mRNA synthesis. Ubiquit in did not affect the degradation of TNF-alpha mRNA and TNF-alpha. In the p resence of LPS, extracellular accumulation of TNF-alpha by ubiquitin was tw ice than those by LPS, but intracellular accumulation of TNF-alpha produced by ubiquitin with LPS or by LPS had no difference. These data indicate tha t ubiquitin might induce TNF-alpha accumulation mainly by up-regulation of the TNF-alpha gene transcription. Although extracellular functions of ubiqu itin remain largely unknown, we postulate that ubiquitin might be involved in the modulatory mechanisms of immune response, (C) 1999 Elsevier Science B.V. All rights reserved.