Marra F, Choudhury G G, Abboud H E
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7882, USA.
J Clin Invest. 1996 Sep 1;98(5):1218-30. doi: 10.1172/JCI118905.
Immunomodulatory cytokines and growth factors act in a complex network to regulate diverse biologic processes. Pre-treatment of two types of human vascular pericytes, liver fat-storing cells or glomerular mesangial cells, with IFN-gamma dramatically enhanced DNA synthesis in response to PDGF or EGF. IFN-gamma by itself had very little effect on DNA synthesis. At least 24-h exposure of the cells to IFN-gamma is required for enhancement of growth factor-induced mitogenesis. IFN-gamma pretreatment did not influence PDGF or EGF receptor autophosphorylation, activation of phospholipase Cgamma1, and phosphatidylinositol 3-kinase, or mitogen-activated protein kinase activity. However, IFN-gamma pretreatment markedly potentiated the DNA binding activity of STAT1alpha in response to PDGF or EGF. Incubation of cells with antisense oligonucleotides targeting STATlalpha mRNA resulted in inhibition of DNA synthesis induced by the combination of IFN-gamma and PDGF or EGF. These data indicate that interaction between IFN-gamma and growth factors at the level of STAT1alpha results in increased DNA synthesis, and establish a role for STAT1alpha in this important biologic function of growth factors.
免疫调节细胞因子和生长因子在一个复杂的网络中发挥作用，以调节多种生物学过程。用γ干扰素对两种类型的人血管周细胞、肝贮脂细胞或肾小球系膜细胞进行预处理，可显著增强其对血小板衍生生长因子（PDGF）或表皮生长因子（EGF）的DNA合成反应。γ干扰素本身对DNA合成的影响很小。细胞至少需要暴露于γ干扰素24小时才能增强生长因子诱导的有丝分裂。γ干扰素预处理不影响PDGF或EGF受体的自身磷酸化、磷脂酶Cγ1以及磷脂酰肌醇3激酶的激活，也不影响丝裂原活化蛋白激酶的活性。然而，γ干扰素预处理能显著增强细胞对PDGF或EGF反应时信号转导和转录激活因子1α（STAT1α）的DNA结合活性。用针对STAT1α mRNA的反义寡核苷酸孵育细胞，可抑制由γ干扰素与PDGF或EGF联合诱导的DNA合成。这些数据表明，γ干扰素与生长因子在STAT1α水平上的相互作用导致DNA合成增加，并确立了STAT1α在生长因子这一重要生物学功能中的作用。
