Costelloe E O, Stacey K J, Antalis T M, Hume D A
Department of Biochemistry, Centre for Molecular and Cellular Biology, University of Queensland, Australia.
J Leukoc Biol. 1999 Jul;66(1):172-82. doi: 10.1002/jlb.66.1.172.
We investigate the regulation of plasminogen activator inhibitor-2 (PAI-2) in murine macrophages. PAI-2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage-like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor alpha or interferon-beta (IFN-beta). PAI-2 mRNA levels generally varied inversely from those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression in cells treated subsequently with LPS. Expression of PAI-2 was distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose response, and sensitivity to co-stimulation with IFN-gamma. Induction of PAI-2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI-2 is discussed in terms of a possible role in LPS-induced pathology such as septicemia.
我们研究了小鼠巨噬细胞中纤溶酶原激活物抑制剂-2（PAI-2）的调控机制。在原代细胞和巨噬细胞样细胞系中，细菌脂多糖（LPS）可诱导PAI-2 mRNA的表达。有证据表明自分泌因子发挥了作用，其中包括环氧化酶产物，但不包括细胞因子肿瘤坏死因子α或干扰素-β（IFN-β）。PAI-2 mRNA水平通常与其靶标尿激酶型纤溶酶原激活物（uPA）的水平呈负相关，并且诱导uPA的巨噬细胞生长因子CSF-1在随后用LPS处理的细胞中抑制PAI-2的表达。就诱导时间进程、LPS剂量反应以及对IFN-γ共刺激的敏感性而言，PAI-2的表达与其他LPS诱导基因的表达不同。细胞系RAW 264亚克隆中PAI-2 mRNA的诱导并不一致，这反映了亲代细胞系中的异质性表达。本文根据PAI-2在诸如败血症等LPS诱导的病理过程中可能发挥的作用，对其表达模式进行了讨论。
