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Dynamic production of tumour necrosis factor‐α (TNF‐α) messenger RNA, intracellular and extracellular TNF‐α by murine macrophages and possible association with protein tyrosine phosphorylation of STAT1α and ERK2 as an early signal
Author(s) -
ZHENG Z. M.,
SPECTER S.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.513591.x
Subject(s) - extracellular , tumor necrosis factor alpha , intracellular , phosphorylation , messenger rna , tyrosine , stat1 , tyrosine phosphorylation , microbiology and biotechnology , biology , cancer research , chemistry , immunology , biochemistry , gene
Tumour necrosis factor‐α (TNF‐α), 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 STAT1α and ERK2 occurred as an immediate early signal, whereas maximum TNF‐α mRNA transcription appeared at 3 hr, precursor TNF‐α formation at 3 to 4 hr, and TNF‐α release at 5 to 6 hr after stimulation of an RPMI‐1640‐based induction medium containing lipopolysaccharide (100 ng/ml), interferon‐γ (100 U/ml), and 0.5% bovine serum albumin. Herbimycin A, a tyrosine kinase inhibitor, suppresses protein tyrosine phosphorylation of STAT1α and ERK2 and also blocks TNF‐α production by resident peritoneal macrophages from BALB/c mice, suggesting a possible association between protein tyrosine phosphorylation of STAT1α and ERK2 and macrophage activation resulting in TNF‐α production.