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

Abstract Ubiquitin synergistically augmented the production of tumor necrosis factor alpha (TNF-α) in the presence of lipopolysaccharide (LPS) in murine macrophage cell line RAW 264.7. To investigate the mechanism of this augmentation, we analyzed the effect of ubiquitin during TNF-α mRNA synthesis and degradation, and TNF-α degradation on RAW 264.7 cells stimulated by LPS. It is found that ubiquitin augmented TNF-α mRNA synthesis. Ubiquitin did not affect the degradation of TNF-α mRNA and TNF-α. In the presence of LPS, extracellular accumulation of TNF-α by ubiquitin was twice than those by LPS, but intracellular accumulation of TNF-α produced by ubiquitin with LPS or by LPS had no difference. These data indicate that ubiquitin might induce TNF-α accumulation mainly by up-regulation of the TNF-α gene transcription. Although extracellular functions of ubiquitin remain largely unknown, we postulate that ubiquitin might be involved in the modulatory mechanisms of immune response.