Regulation of interleukin-8 expression in melanoma-stimulated neutrophil inflammatory response

Regulation of interleukin-8 expression in melanoma-stimulated neutrophil inflammatory response
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DOI:
10.1016/j.yexcr.2006.10.030
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发表时间:
2007-02-01
影响因子:
3.7
通讯作者:
Dong, Cheng
Dong, Cheng
中科院分区:
医学3区
文献类型:
--
作者:
Peng, Hsin-Hsin;Liang, Shile;Dong, Cheng

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炎症促进肿瘤进展,包括转移。白细胞介素 8 (IL-8) 是一种趋化因子,可调节多形核中性粒细胞 (PMN) 动员和活性,我们假设该细胞因子影响肿瘤行为。我们已经证明,IL-8 对于流动条件下 PMN 介导的黑色素瘤外渗至关重要。此外,与黑色素瘤细胞共培养后,PMN 中的 IL-8 上调。黑色素瘤细胞在 PMN 中诱导 I kappa B-alpha 降解,表明 NF-kappa B 信号在 PMN 中活跃。此外,PMN 中 IL-8 的产生依赖于 NF-κ B。我们进一步发现,PMN-黑色素瘤共培养物中的白细胞介素 6 (IL-6) 和白细胞介素 1 β (IL-1 β) 协同促进中性粒细胞中 I kappa B-α 的降解和 IL-8 的合成。总而言之,这些发现表明,黑色素瘤细胞通过激活 NF-κ B 诱导 PMN 分泌 IL-8,并提出了一种模型,其中这种相互作用促进了有利于转移的微环境。 (c) 2006 Elsevier Inc. 保留所有权利。
Inflammation facilitates tumor progression including metastasis. Interleukin-8 (IL-8) is a chemokine that regulates polymorphonuclear neutrophil (PMN) mobilization and activity and we hypothesize that this cytokine influences tumor behavior. We have demonstrated that IL-8 is crucial for PMN-mediated melanoma extravasation under flow conditions. In addition, IL-8 is up-regulated in PMNs upon co-culturing with melanoma cells. Melanoma cells induce I kappa B-alpha degradation in PMNs indicating that NF-kappa B signaling is active in PMNs. Furthermore, the production of IL-8 in PMNs is NF-kappa B dependent. We have further identified that interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) from PMN-melanoma co-cultures synergistically contribute to I kappa B-alpha degradation and IL-8 synthesis in PMNs. Taken together, these findings show that melanoma cells induce PMNs to secrete IL-8 through activation of NF-kappa B and suggest a model in which this interaction promotes a microenvironment that is favorable for metastasis. (c) 2006 Elsevier Inc. All rights reserved.