Ricin induces IL-8 secretion from human monocyte/macrophages by activating the p38 MAP kinase pathway
Ricin induces IL-8 secretion from human monocyte/macrophages by activating the p38 MAP kinase pathway
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DOI：
10.1016/j.molimm.2005.11.002
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发表时间：
2006-04-01
影响因子：
3.6
通讯作者：
Mantis, NJ
中科院分区：
文献类型：
--
作者：
Gonzalez, TV;Farrant, SA;Mantis, NJ
多形核白细胞（PMN）浸润是蓖麻毒素诱导的粘膜炎症的标志，但参与启动这一反应的细胞过程仍不清楚。在这项研究中，我们报告说，蓖麻毒素刺激人单核细胞/巨噬细胞系28 SC分泌IL-8，一种有效的中性粒细胞趋化因子。响应蓖麻毒素的IL-8释放是剂量和时间依赖性的。28 SC细胞暴露于甲醛灭活的全毒素或蓖麻毒素B亚基时不分泌IL-8。布雷菲德菌素A可阻断IL-8的诱导作用。其抑制蓖麻毒素易位到胞质溶胶中。正如从文献中预测的，我们观察到升高水平的p38丝裂原活化蛋白激酶（MAPK），IL-8的转录后调节因子，早在蓖麻毒素暴露后3它在28 SC细胞。用已知的p38 MAPK抑制剂吡啶咪唑类似物SB 203580处理28 SC细胞，抑制蓖麻毒素介导的IL-8释放。我们的结论是，蓖麻毒素刺激人单核细胞/巨噬细胞产生IL-8的p38 MAPK通路的激活，提高的可能性，p38 MAPK抑制剂可能作为治疗剂，以抑制与蓖麻毒素中毒相关的粘膜炎症。(c)2005爱思唯尔有限公司保留所有权利。
Polymorphonuclear cell (PMN) infiltration is a hallmark of ricin-induced mucosal inflammation, yet the cellular processes involved in initiating this reaction remain undefined. In this study we report that ricin stimulates the human monocyte/macrophages cell line 28SC to secrete IL-8, a potent PMN chemoattractant. IL-8 release in response to ricin was both dose- and time-dependent. 28SC cells did not secrete IL-8 when exposed to formaldehyde-inactivated holotoxin or ricin B subunit. Furthermore, IL-8 induction could be blocked by brefeldin A. which inhibits ricin translocation into the cytosol. As predicted from the literature, we observed elevated levels of p38 mitogen activated protein kinase (MAPK), a post-transcriptional regulator of IL-8, in 28SC cells as early as 3 It after ricin exposure. Treatment of 28SC cells with the pyridylimidizole analogue SB203580, a known inhibitor of p38 MAPK, suppressed ricin-mediated IL-8 release. We conclude that ricin stimulates human monocyte/macrophages to produce IL-8 by activation of the p38 MAPK pathway, raising the possibility that p38 MAPK inhibitors may potentially serve as therapeutic agents to suppress mucosal inflammation associated with ricin intoxication. (c) 2005 Elsevier Ltd. All rights reserved.