Zheng Z M, Specter S
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, FL, USA.
Immunology. 1996 Apr;87(4):544-50. doi: 10.1046/j.1365-2567.1996.513591.x.
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.
肿瘤坏死因子-α（TNF-α）是免疫和炎症反应中的一种重要介质，是活化巨噬细胞释放的主要细胞因子之一。本研究表明，在巨噬细胞活化过程中，STAT1α和ERK2的蛋白酪氨酸磷酸化作为即时早期信号出现，而在含有脂多糖（100 ng/ml）、干扰素-γ（100 U/ml）和0.5%牛血清白蛋白的基于RPMI-1640的诱导培养基刺激后，TNF-α mRNA转录在3小时达到最大值，前体TNF-α在3至4小时形成，TNF-α在5至6小时释放。酪氨酸激酶抑制剂赫比霉素A可抑制STAT1α和ERK2的蛋白酪氨酸磷酸化，也可阻断BALB/c小鼠腹腔驻留巨噬细胞产生TNF-α，这表明STAT1α和ERK2的蛋白酪氨酸磷酸化与巨噬细胞活化导致TNF-α产生之间可能存在关联。
