Dynamic production of tumour necrosis factor-alpha (TNF-alpha) messenger RNA, intracellular and extracellular TNF-alpha by murine macrophages and possible association with protein tyrosine phosphorylation of STAT1 alpha and ERK2 as an early signal.
Tumour necrosis factor-alpha (TNF-alpha), an important mediator in both immune and inflammation responses, is one of the major cytokines released by activated macrophages. The present study shows that, during macrophage activation, protein tyrosine phosphorylation of STAT1 alpha and ERK2 occurred as an immediate early signal, whereas maximum TNF-alpha mRNA transcription appeared at 3 hr, precursor TNF-alpha formation at 3 to 4 hr, and TNF-alpha release at 5 to 6 hr after stimulation of an RPMI-1640-based induction medium containing lipopolysaccharide (100 ng/ml), interferon-gamma (100 U/ml), and 0.5% bovine serum albumin. Herbimycin A, a tyrosine kinase inhibitor, suppresses protein tyrosine phosphorylation of STAT1 alpha and ERK2 and also blocks TNF-alpha production by resident peritoneal macrophages from BALB/c mice, suggesting a possible association between protein tyrosine phosphorylation of STAT1 alpha and ERK2 and macrophage activation resulting in TNF-alpha production.
Zheng
Z M
ZM
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, FL, USA.
Specter
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D000818:Animals; D015152:Blotting, Northern; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015151:Immunoblotting; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D007700:Kinetics; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; C494228:Isgf3g protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1