Cisplatin primes murine peritoneal macrophages for enhanced expression of nitric oxide, proinflammatory cytokines, TLRs, transcription factors and activation of MAP kinases upon co-incubation with L929 cells
Cisplatin primes murine peritoneal macrophages for enhanced expression of nitric oxide, proinflammatory cytokines, TLRs, transcription factors and activation of MAP kinases upon co-incubation with L929 cells
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DOI：
10.1016/j.imbio.2008.07.012
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发表时间：
2009-03-01
期刊：
影响因子：
2.8
通讯作者：
Shrivastava, Anju
中科院分区：
文献类型：
--
作者：
Chauhan, Puja;Sodhi, Ajit;Shrivastava, Anju
顺铂是一种化疗药物，也可以作为生物反应调节剂。顺铂（10 μ g/ml）处理巨噬细胞24小时激活它们以产生增加量的一氧化氮（NO）、ROI、促炎细胞因子并表现出增加的杀肿瘤活性，这可能是或可能不是接触介导的。在本研究中，我们报告说，用顺铂短时间处理巨噬细胞2小时足以使它们更容易接受与肿瘤细胞的相互作用。用顺铂预处理2 h并与L929细胞共孵育的巨噬细胞产生增强的NO、TNF-α、IL-1 β、IL-12和IFN-γ。NO、TNF-α、IL-1 β、IL-12和IFN-γ的产生在共孵育24 h时最大。在与L929细胞共孵育12至24小时之间，观察到顺铂预处理的巨噬细胞中iNOS、TNF-α、IL-1 β、IL-12和IFN-γ基因的转录增强。顺铂处理的巨噬细胞与L929细胞共孵育也表达Toll样受体（TLR）-2和TLR-4基因及其蛋白的转录增强。观察到顺铂预处理的巨噬细胞与L929细胞共孵育后显示出有丝分裂原活化蛋白（MAP）激酶和NF-κ B的激活。药理学抑制剂如PD 98059、SB 202190和wortmannin强烈抑制NO和促炎细胞因子的产生，提示p42/44、p38 MAPK和PI 3 K在上述过程中可能起作用。c-Jun氨基末端激酶（JNK）抑制剂SP 600125在抑制NO和促炎细胞因子的产生方面效果较差。因此，数据表明，用顺铂预处理巨噬细胞使它们在生物学上对与L929细胞的相互作用更敏感并被激活。(C)2008年Elsevier GmbH。All rights reserved.
Cisplatin, a chemotherapeutic drug, may also act as a biological response modifier. Cisplatin (10 mu g/ml) treatment of macrophages for 24h activates them to produce enhanced amounts of nitric oxide (NO), ROI, proinflammatory cytokines and exhibit increased tumoricidal activity, which may or may not be contact mediated. In the present investigation, we report that the treatment of macrophages with cisplatin for a short period of 2 h is sufficient to make them more receptive to interaction with tumor cells. Macrophages pretreated with cisplatin for 2 h, and co-incubated with L929 cells, produced enhanced NO, TNF-alpha, IL-1 beta, IL-12 and IFN-gamma. Production of NO, TNF-alpha, IL-1 beta, IL-12 and IFN-gamma was maximum at 24h of co-incubation. Enhanced transcription of iNOS, TNF-alpha, IL-1 beta, IL-12 and IFN-gamma genes in cisplatin-pretreated macrophages were observed between 12 and 24h of co-incubation with L929 cells. Cisplatin-treated macrophages on co-incubation with L929 cells also expressed enhanced transcription of Toll-like receptor (TLR)-2 and TLR-4 genes and their proteins. It is observed that cisplatin-pretreated macropbages on co-incubation with L929 cells showed activation of mitogen-activated protein (MAP) kinases and NF-kappa B. Pharmacological inhibitors like PD98059, SB202190 and wortmannin strongly inhibited the production of NO and proinflammatory cytokines suggesting the probable role of p42/44, p38 MAPK and PI3K in the above process. The c-Jun amino terminal kinase (JNK) inhibitor SP600125 was less effective in inhibiting the production of NO and proinflammatory cytokines. The data thus suggests that pretreatment of macrophages with cisplatin makes them biologically more responsive to interaction with L929 cells and become activated. (C) 2008 Elsevier GmbH. All rights reserved.