Orlicek S L, Meals E, English B K
Crippled Children's Foundation Research Center at LeBonheur Children's Medical Center, Memphis, Tennessee 38103, USA.
J Infect Dis. 1996 Sep;174(3):638-42. doi: 10.1093/infdis/174.3.638.
The temporal requirements for tyrosine phosphorylation in the induction of tumor necrosis factor (TNF) and inducible nitric oxide synthase (NOS) were compared in the routine macrophage cell line RAW 264.7. Preincubation of RAW 264.7 cells with herbimycin A or genistein (but not with either of three tyrphostins tested) significantly blocked TNF and NOS production on exposure of these cells to combinations of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). The addition of either genistein or herbimycin A to RAW 264.7 cell cultures 1-6 It after stimulation with LPS and IFN-gamma had little or no effect on TNF production but markedly inhibited NOS protein accumulation. Together these data indicate that tyrosine kinase inhibitors block NOS production at a point well downstream of the initial wave of LPS- and IFN-gamma-mediated protein tyrosine phosphorylation.
在常规巨噬细胞系RAW 264.7中比较了诱导肿瘤坏死因子（TNF）和诱导型一氧化氮合酶（NOS）时酪氨酸磷酸化的时间要求。用除莠霉素A或染料木黄酮（但不是三种受试酪氨酸磷酸化抑制剂中的任何一种）预孵育RAW 264.7细胞，可显著阻断这些细胞在暴露于脂多糖（LPS）和干扰素-γ（IFN-γ）组合时TNF和NOS的产生。在用LPS和IFN-γ刺激RAW 264.7细胞培养物1-6小时后添加染料木黄酮或除莠霉素A对TNF产生几乎没有影响，但显著抑制NOS蛋白积累。这些数据共同表明，酪氨酸激酶抑制剂在LPS和IFN-γ介导的蛋白酪氨酸磷酸化初始波的下游位点阻断NOS的产生。
