Dimethylnitrosamine (DMN)-induced IL-1 beta, TNF-alpha, and IL-6 inflammatory cytokine expression.
Dimethylnitrosamine (DMN)-induced IL-1 beta, TNF-alpha, and IL-6 inflammatory cytokine expression.
复制标题
二甲基亚硝胺 (DMN) 诱导 IL-1 β、TNF-α 和 IL-6 炎症细胞因子表达。
DOI：
10.1016/0041-008x(92)90151-h
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发表时间：
1992
影响因子：
3.8
通讯作者：
Myers,MJ
中科院分区：
文献类型：
--
作者：
Schook,LB;Lockwood,JF;Yang,SD;Myers,MJ
小鼠暴露于二甲基亚硝胺（DMN）后，免疫功能发生了变化。特别是，在细胞介导的免疫反应的变化导致慢性DMN暴露在体内。由于细胞因子是有效的免疫调节肽，因此进行实验以确定DMN暴露是否导致血清传播的炎性细胞因子的诱导。将动物每24小时暴露于媒介物（PBS）或DMN（5.0 mg/kg），持续14天。在首次暴露后0、1、2、3、6、12和24小时从个体小鼠获得血清和肝脏样品，在每日DMN暴露前每24小时收集额外样品。然后使用生物学或免疫学测定法分析血清的IL-1β、IL-3、IL-6、CSF-1、GM-CSF和TNF-α活性。此外，使用溶液杂交/RNA酶保护试验探测肝脏总细胞RNA对IL-1β转录物的诱导。在DMN暴露后2小时内观察到IL-1β、IL-6和TNF-α血清活性，即使维持DMN暴露，这些血清活性也在3天时恢复至溶剂对照水平。仅在GM-CSF中观察到细胞因子活性的慢性表达（72小时后）。通过溶液杂交观察到溶剂和DMN处理动物中IL-1β转录物的快速诱导（1小时内）。然而，在暴露后3小时，载体处理的动物中的转录水平降低，而在DMN处理的动物中保持升高6小时。这些结果表明，DMN在体内暴露诱导：（1）血清传播的细胞因子活性的表达，和（2）肝组织中IL-1β的转录。
Altered immune functions have been demonstrated in mice following exposure to dimethylnitrosamine (DMN). In particular, changes in cell-mediated immune responses resulted from chronic DMN exposure in vivo. Since cytokines are potent immunoregulatory peptides, experiments were performed to determine whether DMN exposure results in the induction of serum-borne inflammatory cytokines. Animals were exposed to either vehicle (PBS) or DMN (5.0 mg/kg) every 24 hr for 14 days. Serum and liver samples were obtained from individual mice at 0, 1, 2, 3, 6, 12, and 24 hr following the first exposure, with additional samples collected every 24 hr preceeding the daily DMN exposure. Sera were then analyzed for IL-1β, IL-3, IL-6, CSF-1, GM-CSF, and TNF-α activities using either biological or immunological assays. In addition, liver total cellular RNA was probed for the induction of IL-1β transcripts using the solution hybridization/RNase protection assay. IL-1β, IL-6, and TNF-α serum activities were observed within 2 hr of DMN exposure and returned to vehicle control levels by 3 days even though DMN exposure was maintained. Chronic expression of cytokine activity (after 72 hr) was only observed for GM-CSF. A rapid induction of IL-1β transcripts (within 1 hr) in both vehicle and DMN-treated animals was observed by solution hybridization. However, by 3 hr postexposure, transcript levels decreased in the vehicle-treated animals while remaining elevated in the DMN-treated animals for 6 hr. These results demonstrated that DMN exposure in vivo induced: (1) the expression of serum-borne cytokine activities, and (2) IL-1β transcription in liver tissue.