Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.
Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.
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DOI：
10.12659/msm.895739
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发表时间：
2016-02-04
期刊：
影响因子：
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通讯作者：
Fujino Y
中科院分区：
文献类型：
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作者：
Yamamoto S;Ohta N;Matsumoto A;Horiguchi Y;Koide M;Fujino Y
氟哌啶醇是一种镇静剂，用于治疗精神障碍的症状和镇静激动和谵妄患者。值得注意的是，氟哌啶醇已被认为通过未知的机制抑制免疫反应。我们假设镇静剂通过NF-κB调节免疫反应。使用流式细胞术，我们分析了氟哌啶醇对RAW 264细胞和骨髓来源的原代巨噬细胞中CD 80和CD 86表达的影响。采用酶联免疫吸附试验测定白细胞介素（IL）-1β、IL-6和IL-12 p40的分泌。此外，NF-κB活化使用基于分泌性胚胎碱性磷酸酶的报告基因测定进行评价。最后，使用合成拮抗剂来鉴定介导氟哌啶醇作用的多巴胺受体。氟哌啶醇抑制NF-κB活化，从而抑制CD 80的表达以及IL-1β、IL-6和IL-12 p40的分泌。CD 80和IL-6水平类似地被D2样受体拮抗剂减弱，但不被D1样受体拮抗剂减弱。这些数据有力地表明，氟哌啶醇通过多巴胺D2受体抑制NF-κB信号传导来抑制免疫应答。
Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-κB signaling via the dopamine D2 receptor.