Inhibitory effect of 3,4-dichloropropionaniline on cytokine production by macrophages is associated with LPS-mediated signal transduction

Inhibitory effect of 3,4-dichloropropionaniline on cytokine production by macrophages is associated with LPS-mediated signal transduction
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DOI:
10.1002/jlb.61.6.745
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发表时间:
1997-06-01
影响因子:
5.5
通讯作者:
Barnett, JB
Barnett, JB
中科院分区:
医学3区
文献类型:
--
作者:
Xie, YC;Schafer, R;Barnett, JB

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我们以前的研究表明,在体内和体外,3,4-二氯丙酰苯胺(丙胺)暴露都能抑制脂多糖(LPS)刺激后黏附的硫代乙酸乙酯诱导的巨噬细胞产生白介素6(IL-6)和肿瘤坏死因子(TNF)。在本研究中,我们报道了丙醇以浓度依赖的方式减少IL-6和TNF-α的信息传递,但不影响细胞因子mRNA的稳定性。此外,在相对较短的时间内暴露于丙醇后,巨噬细胞IL-6和TNF的产生显著减少。细胞内钙水平的测定表明,丙醇处理的巨噬细胞抑制了内毒素诱导的钙释放,但不影响内毒素与巨噬细胞的结合。1,4,5-三磷酸肌醇(IP3)测定表明丙醇显著增加巨噬细胞中IP3的水平和持续时间。这些结果提示丙烷对巨噬细胞细胞因子产生的抑制作用与内毒素介导的巨噬细胞信号转导的早期阶段有关。
Our previous studies demonstrated that both in vivo and in vitro 3,4-dichloro-propionanilide (propanil) exposure inhibited interleukin-6 (IL-6) and tumor necrosis factor (TNF) production by adherent thioglycollate-elicited peritoneal cells (macrophages) after lipopolysaccharide (LPS) stimulation. In this study, we report that IL-6 and TNF-alpha message is reduced by propanil in a concentration-dependent pattern, yet the stability of cytokine mRNA is not affected, hn addition, exposure of macrophages to propanil after a relatively short period of LPS stimulation significantly reduced the production of IL-6 and TNF, Determination of the intracellular Ca2+ levels demonstrates that LPS-induced Ca2+ release is abrogated in propanil-treated macrophages, However, the binding of LPS to macrophages is not affected, Measurement of inositol 1,4,5-triphosphate (IP3) demonstrates that propanil significantly increases the level and the duration of IP3 in macrophages, These results suggest that the inhibitory effect of propanil on macrophage cytokine production is associated with the early stages of LPS-mediated signal transduction in macrophages.