Nitric oxide inhibits LPS-induced IL-6 production in enterocytes.
Nitric oxide inhibits LPS-induced IL-6 production in enterocytes.
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一氧化氮抑制肠细胞中 LPS 诱导的 IL-6 产生。
DOI：
10.1006/jsre.1995.1090
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
Hasselgren,PO
中科院分区：
文献类型：
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作者：
Meyer,TA;Tiao,GM;James,JH;Noguchi,Y;Ogle,CK;Fischer,JE;Hasselgren,PO
在最近的研究中，脂多糖 (LPS) 刺激培养的肠细胞中白细胞介素 6 (IL-6) 的产生。在其他细胞类型中，IL-6 的产生受到一氧化氮 (NO) 的抑制。我们测试了这样的假设：肠上皮细胞中 LPS 诱导的 IL-6 产生至少部分受 NO 调节。将 IEC-6 细胞（大鼠肠上皮细胞系）与 LPS (1-10 μg/ml)、NO 合酶抑制剂 N-ω-硝基-L-精氨酸 (NNA，3300 μM)、L-精氨酸 (10 mM)、NO 供体硝普钠 (SNP，0.5-1 μM) 或单独培养基作为对照的不同组合培养 3 天。通过 B9 鼠杂交瘤生物测定法测定培养基中的 IL-6 水平。亚硝酸盐是 NO 代谢的稳定终产物，通过 HPLC 进行测量。进行 PCR 以确定 IEC-6 细胞中诱导型 NO 合酶 (iNOS) mRNA 表达。用 LPS 处理 IEC-6 细胞可刺激 IL-6 的产生。 NNA 以剂量依赖性方式进一步增加 LPS 诱导的 IL-6 产生。 NNA 的这种作用通过添加 L-精氨酸而消除。 SNP 导致 IL-6 产量呈剂量依赖性下降。 LPS 处理后，亚硝酸盐的产生量呈剂量依赖性增加。 PCR 显示，给予 1 μg/ml LPS 后，IEC-6 细胞中 iNOS mRNA 表达增加。结果表明，NO 抑制肠上皮细胞中 LPS 诱导的 IL-6 产生。 NO 可能是脓毒症和内毒素血症期间肠道细胞因子反应的重要调节因子。
In recent studies, production of interleukin-6 (IL-6) in cultured enterocytes was stimulated by lipolysaccharide (LPS). In other cell types, IL-6 production was inhibited by nitric oxide (NO). We tested the hypothesis that LPS-induced IL-6 production in the enterocyte is regulated, at least in part, by NO. IEC-6 cells (a rat intestinal epithelial cell line) were cultured for 3 days with different combinations of LPS (1-10 μg/ml), the NO synthase inhibitor N-ω-nitro-L-arginine (NNA, 3300 μM), L -arginine (10 mM), the NO donor sodium nitroprusside (SNP, 0.5-1 μM), or medium alone as control. IL-6 levels in the culture medium were determined by the B9 murine hybridoma bioassay. Nitrite, a stable end product of NO metabolism, was measured by HPLC. PCR was performed to determine inducible NO synthase (iNOS) mRNA expression in the IEC-6 cells. Treatment of IEC-6 cells with LPS stimulated IL-6 production. LPS-induced IL-6 production was further increased by NNA in a dose-dependent fashion. This effect of NNA was abolished by the addition of L-arginine. SNP caused a dose-dependent decrease in IL-6 production. Nitrite production was increased in a dose-dependent fashion after LPS treatment. PCR revealed an increase in iNOS mRNA expression in IEC-6 cells after administration of 1 μg/ml LPS. The results suggest that NO inhibits LPS-induced IL-6 production in the enterocyte. NO may be an important regulator of intestinal cytokine response during sepsis and endotoxemia.