Goodman A R, Levy D E, Reis L F, Vilcek J
Department of Microbiology, New York University School of Medicine, NY 10016, USA.
J Leukoc Biol. 2000 Mar;67(3):387-95. doi: 10.1002/jlb.67.3.387.
Tumor necrosis factor (TNF)-stimulated gene 14 (TSG-14, also termed PTX3) encodes a secreted glycoprotein whose carboxy-terminal half shares sequence similarity with the pentraxin family of acute phase proteins (C-reactive protein and serum amyloid P component). We compared TSG-14 mRNA expression in cultures of murine BALB/c 3T3 fibroblasts and thioglycollate-elicited peritoneal macrophages. TNF and interleukin-1 (IL-1) potently induced TSG-14 expression in 3T3 fibroblasts but not in peritoneal macrophages. Lipopolysaccharide (LPS) elicited TSG-14 expression in both cell types, but induction in 3T3 cells and macrophages showed several distinct characteristics. Whereas in 3T3 fibroblasts TSG-14 mRNA was rapidly up-regulated by LPS, expression in macrophages was substantially delayed. Furthermore, cycloheximide greatly reduced LPS-induced TSG-14 mRNA up-regulation in macrophages but not in 3T3 cells. Finally, interferon-gamma (IFN-gamma; but not IFN-alpha/beta) inhibited LPS-induced TSG-14 expression in macrophages and not in 3T3 fibroblasts. The antioxidant pyrrolidine dithiocarbamate inhibited LPS-induced nuclear factor-kappaB (NF-kappaB) activation and TSG-14 expression in macrophages. In contrast, IFN-gamma did not inhibit NF-kappaB function as measured by IkappaB-alpha and IkappaB-beta degradation, IkappaB-alpha resynthesis, or electrophoretic mobility shift analysis. Inhibition of LPS-induced TSG-14 mRNA expression by IFN-gamma in macrophages was also observed in the presence of cycloheximide and in cells from STAT1 null mice, suggesting that IFN-gamma inhibits TSG-14 expression through an unconventional mechanism.
肿瘤坏死因子（TNF）刺激基因14（TSG - 14，也称为PTX3）编码一种分泌型糖蛋白，其羧基末端的一半与急性期蛋白的五聚体家族（C反应蛋白和血清淀粉样蛋白P成分）具有序列相似性。我们比较了TSG - 14 mRNA在小鼠BALB/c 3T3成纤维细胞培养物和巯基乙酸诱导的腹腔巨噬细胞中的表达。TNF和白细胞介素 - 1（IL - 1）能有效诱导3T3成纤维细胞中TSG - 14的表达，但不能诱导腹腔巨噬细胞中的表达。脂多糖（LPS）能诱导这两种细胞类型中TSG - 14的表达，但在3T3细胞和巨噬细胞中的诱导表现出几个不同的特征。在3T3成纤维细胞中，LPS能迅速上调TSG - 14 mRNA的表达，而在巨噬细胞中的表达则显著延迟。此外，放线菌酮能极大地降低LPS诱导的巨噬细胞中TSG - 14 mRNA的上调，但对3T3细胞没有影响。最后，干扰素 - γ（IFN - γ；而不是IFN - α/β）能抑制LPS诱导的巨噬细胞中TSG - 14的表达，而对3T3成纤维细胞没有影响。抗氧化剂吡咯烷二硫代氨基甲酸盐能抑制LPS诱导的巨噬细胞中核因子 - κB（NF - κB）的激活和TSG - 14的表达。相比之下，通过IkappaB - α和IkappaB - β的降解、IkappaB - α的再合成或电泳迁移率变动分析来衡量，IFN - γ并没有抑制NF - κB的功能。在放线菌酮存在的情况下以及在STAT1基因敲除小鼠的细胞中，也观察到IFN - γ对LPS诱导的巨噬细胞中TSG - 14 mRNA表达的抑制作用，这表明IFN - γ通过一种非常规机制抑制TSG - 14的表达。
