Regulation of interleukin-8 expression in human prostate cancer cells by insulin-like growth factor-I and inflammatory cytokines
Regulation of interleukin-8 expression in human prostate cancer cells by insulin-like growth factor-I and inflammatory cytokines
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DOI：
10.1016/j.ghir.2007.04.004
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发表时间：
2007-10-01
影响因子：
1.4
通讯作者：
Coppens, Astrid
中科院分区：
文献类型：
--
作者：
Kooijman, Ron;Himpe, Eddy;Coppens, Astrid
目的：由于血清IGF-I水平与前列腺癌的风险有关，白细胞介素(IL)-6和IL-8等细胞因子与前列腺癌的进展有关，我们研究了IGF-I对前列腺癌细胞中IL-6和IL-8表达的影响。设计：为了研究igf -1对前列腺癌细胞中细胞因子表达的调节作用，我们使用已建立的雄激素依赖性（LNCaP）和雄激素非依赖性细胞系（DU-145和PC-3）的细胞培养。结果：我们发现IGF-I刺激DU-145细胞IL-8 mRNA的表达和分泌，而IL-6的分泌几乎不受影响。IGF-I与IL-1 β协同增强IL-8表达，但不与肿瘤坏死因子(TNF) α协同。同样，在IL-8启动子活性上，IGF-I与IL-1 β发挥协同作用，但与TNF α不起协同作用。虽然IGF-I刺激了Akt（蛋白激酶B）和细胞外调节激酶（ERK）的磷酸化，但IGF-I对IL-8表达的影响仅被MAPK/ERK激酶（MEK）的药理抑制剂U0126抑制，而不被Akt的上游激活剂磷脂酰肌醇-3激酶（PI3K）的抑制所抑制。结论：我们的研究结果表明，IGF-I通过MEK-ERK途径刺激DU-145细胞中IL-8的表达，至少部分是通过增强转录活性来实现的。这一发现与我们在LNCaP和PC-3细胞中观察到的IGF-I不影响细胞因子分泌和ERK磷酸化一致。IL-8是否介导了IGF-I对前列腺癌细胞的某些作用，以及前列腺癌细胞对IGF-I的差异反应性是否与前列腺癌的某些阶段有关，目前尚不清楚。(c) 2007 Elsevier Ltd.版权所有。
Objective: Since serum IGF-I levels are related to risks of prostate cancer and cytokines like interleukin (IL)-6 and IL-8 have been implicated in prostate cancer progression, we investigated the effects of IGF-I on IL-6 and IL-8 expression in the prostate cancer cell.Design: In order to address the regulation by IGF-I of cytokine expression in prostate cancer cells we used cell cultures of established androgen dependent (LNCaP) and androgen-independent cell lines (DU-145 and PC-3).Results: We found that IGF-I stimulates IL-8 mRNA expression and secretion in DU-145 cells, whereas the secretion of IL-6 was hardly affected. IGF-I enhances IL-8 expression in synergy with IL-1 beta, but not with tumour necrosis factor (TNF)alpha. Similarly, on IL-8 promoter activity, IGF-I exerted synergistic effects with IL-1 beta, but not with TNF alpha. Although IGF-I stimulated the phosphorylation of both Akt (protein kinase B) and extracellular-regulated kinase (ERK), the effect of IGF-I at IL-8 expression was inhibited only by U0126, a pharmacological inhibitor of MAPK/ERK kinase (MEK) and not by inhibition of the upstream activator of Akt, phosphatidylinositol-3 kinase (PI3K).Conclusions: Our results indicate that IGF-I stimulates IL-8 expression through the MEK-ERK pathway in DU-145 cells, at least in part, by augmentation of transcriptional activity. This finding is in accordance with our observations that IGF-I did not influence cytokine secretion and phosphorylation of ERK in LNCaP or PC-3 cells. It remains to be established whether IL-8 mediates certain effects of IGF-I on prostate cancer cells and whether differential responsiveness of prostate cancer cells to IGF-I relates to certain stages of prostate cancer. (c) 2007 Elsevier Ltd. All rights reserved.