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 macrophage cell line RAW 264.7. To investigate the mechanism of this augmentation, we analyzed the effect of ubiquitin during TNF-alpha mRNA synthesis and degradation, and TNF-alpha degradation on RAW 264.7 cells stimulated by LPS. It is found that ubiquitin augmented TNF-alpha mRNA synthesis. Ubiquitin did not affect the degradation of TNF-alpha mRNA and TNF-alpha. In the presence of LPS, extracellular accumulation of TNF-alpha by ubiquitin was twice than those by LPS, but intracellular accumulation of TNF-alpha produced by ubiquitin with LPS or by LPS had no difference. These data indicate that ubiquitin might induce TNF-alpha accumulation mainly by up-regulation of the TNF-alpha gene transcription. Although extracellular functions of ubiquitin remain largely unknown, we postulate that ubiquitin might be involved in the modulatory mechanisms of immune response.
Nabika
T
T
Department of Surgery, Shimane Medical University, Izumo 693-8501, Japan.
Terashima
M
M
Momose
I
I
Hosokawa
Y
Y
Nagasue
N
N
Tanigawa
Y
Y
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014452:Ubiquitins / Q000494:pharmacology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014452:Ubiquitins