Identification of genes involved in innate responsiveness to bacterial products by differential display.
Identification of genes involved in innate responsiveness to bacterial products by differential display.
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通过差异展示鉴定涉及对细菌产物的先天反应的基因。
DOI：
10.1006/meth.1998.0694
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Ding,A
中科院分区：
文献类型：
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作者：
Jin,F;Nathan,C;Ding,A
为了探索细菌脂多糖（LPS）的基因调控，我们比较了两种小鼠系的巨噬细胞系的mRNA谱，这两种小鼠系与明显影响其对LPS反应能力的基因座同源。差异显示检测到四个差异表达的转录本。一个转录本编码人分泌性白细胞蛋白酶抑制剂（SLPI）的小鼠同源物，其由LPS低反应巨噬细胞（Lpsd）表达，但不由LPS正常反应细胞（Lpsn）表达。在5种巨噬细胞系中，SLPI的分泌与LPS反应产生一氧化氮（NO）和肿瘤坏死因子α（TNF α）的能力呈负相关。用SLPI稳定转染LPS反应性巨噬细胞抑制LPS诱导的反应。γ干扰素（IFN-γ）可纠正LPS诱导的巨噬细胞对LPS的反应缺陷，抑制LPS诱导的SLPI表达，并恢复LPS对过表达SLPI的巨噬细胞的反应。除了作为LPS反应抑制剂的作用外，小鼠SLPI也是脂磷壁酸反应抑制剂。IL-10和IL-6可显著增强SLPI的表达。SLPI可能是宿主防御革兰氏阴性菌和革兰氏阳性菌的一种重要的趋化因子。
To explore gene regulation by bacterial lipopolysaccharide (LPS), we compared mRNA profiles of macrophage cell lines from two strains of mice congenic for a locus markedly affecting their ability to respond to LPS. Differential display detected four differentially expressed transcripts. One transcript encoded the mouse homolog of human secretory leukocyte protease inhibitor (SLPI), which was expressed by LPS-hyporesponsive macrophage cells (Lpsd) but not by LPS-normoresponsive cells (Lpsn). Among five macrophage cell lines, secretion of SLPI was inversely correlated with ability to produce nitric oxide (NO) and tumor necrosis factor α in response to LPS. Stable transfection of LPS-responsive macrophages with SLPI suppressed LPS-induced responses. Interferon-γ (IFN-γ), which corrects the defective LPS response inLpsdmacrophages, suppressed the LPS-induced expression of SLPI and restored LPS response to SLPI-overexpressing macrophages. Besides its role as a LPS response inhibitor, mouse SLPI is also a lipoteichoic acid response inhibitor. The expression of SLPI was strongly enhanced by interleukin-10 and -6. SLPI may be an important antiinflammatory molecule in host defense against gram-negative and gram-positive bacteria.