Down-regulation of interleukin-8 secretion from Mycobacterium tuberculosis-infected monocytes by interleukin-4 and-10 but not by interleukin-13
Down-regulation of interleukin-8 secretion from Mycobacterium tuberculosis-infected monocytes by interleukin-4 and-10 but not by interleukin-13
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DOI：
10.1128/iai.69.4.2470-2476.2001
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发表时间：
2001-04-01
影响因子：
3.1
通讯作者：
Friedland, JS
中科院分区：
文献类型：
--
作者：
Ameixa, C;Friedland, JS
白细胞介素-8 （IL-8）是一种CXC趋化因子，在结核病肉芽肿形成区域的白细胞募集中起核心作用。在本研究中，我们研究了T(H)2衍生的细胞因子IL-4、IL-10和IL-13对纯化的人单核细胞结核分枝杆菌诱导的IL-8分泌的影响。我们的研究结果表明，IL-4和IL-10对IL-8的分泌有下调作用，并且这种作用是剂量依赖性的。IL-10对分泌的影响大于IL-4，并且结核分枝杆菌感染单核细胞分泌的自身IL-10也下调IL-8的分泌。通过逆转录- pcr分析，下调作用部分是由于IL-8 mRNA积累减少的结果。当1mum - IL-4和IL-10联合使用时，它们在降低IL-8分泌和转录方面具有加性作用；没有行动的协同作用。IL-13对IL-8基因的表达和分泌无明显影响。IL-10而非IL-4的抑制作用与关键激活转录因子NF-kappaB的核结合减少有关。我们首次通过电迁移凝胶位移法发现结核分枝杆菌引起Oct-1的核结合上调。然而，IL-4或IL-10均未改变AP-1和Oct-1的核结合。总之，本研究表明，2型应答在结核分枝杆菌诱导的IL-8表达调控中起重要作用，但不同细胞因子的作用机制不同。
Interleukin-8 (IL-8), a CXC chemokine, has a central role in leukocyte recruitment to areas of granuloma formation in tuberculosis. In the present studies, we investigated the effect of the T(H)2-derived cytokines IL-4, IL-10, and IL-13 on Mycobacterium tuberculosis-induced IL-8 secretion from purified human monocytes. Our results demonstrate that IL-4 and IL-10 have a down-regulatory effect on IL-8 secretion and that this effect is dose dependent. IL-10 has a greater effect than IL-4 on secretion, and autologous IL-10 secreted from M. tuberculosis-infected monocytes also down-regulates IL-8 secretion. The down-regulatory effect is partly a result of reduced IL-8 mRNA accumulation analyzed by reverse transcription-PCR. When combined, 1 muM IL-4 and IL-10 had an additive effect in decreasing IL-8 secretion and transcription; there was no synergy of action. IL-13 did not have any significant effect on IL-8 gene expression or secretion. The inhibitory effect of IL-10 but not of IL-4 is associated with decreased nuclear binding of the key activating transcription factor NF-kappaB. We show for the first time that M. tuberculosis causes up-regulation of nuclear binding of Oct-1 detected by electromobility gel shift assay. However, neither AP-1 nor Oct-1 nuclear binding was altered by IL-4 or IL-10. In summary, this study demonstrates that type 2 responses have an important role in the regulation of M. tuberculosis-induced IL-8 expression but that the mechanisms by which the different cytokines act are distinct.