Enhanced production of tumour necrosis factor alpha (TNF-alpha) by its precursor on the cell surface of primed THP-1 cells.
To clarify the biological significance of tumour necrosis factor alpha (TNF-alpha) precursor, we analysed its expression at the primed and triggered stages using human monocyte-like cell line THP-1. To prime them, THP-1 cells were treated with either recombinant human interferon gamma (rIFN-gamma) or recombinant human tumour necrosis factor alpha (rTNF-alpha). At the primed stage, transient accumulation of TNF-alpha, mRNA and a small amount of 26-KDa TNF-alpha precursor was observed, and the precursor molecule was located on the cell surface. Following treatment of the primed cells with bacterial lipopolysaccharide (LPS), augmentation of transcription of TNF-alpha mRNA and production of a larger amount of TNF-alpha precursor were observed followed by secretion of a larger amount of mature TNF-alpha (17-KDa) than secreted by the unprimed cells (triggered stage). This suggests that with priming THP-1 cells might be changed to a stage where they are ready for production of a larger amount of TNF-alpha at the triggered stage. When either primed or unprimed THP-1 cells were pretreated with anti-TNF-alpha antibody, augmentation of TNF-alpha production by primed THP-1 cells was specifically suppressed, suggesting that TNF-alpha precursor itself may play an important role in the enhancement of TNF-alpha production by the primed macrophages after treatment with LPS.
Tanabe
Y
Y
Biotechnology Research Center, Teikyo University, Kawasaki, Japan.
Kitahara-Tanabe
N
N
Mizuno
D
D
Soma
G I
GI
D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000494:pharmacology
D011498:Protein Precursors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma