Interleukin-18may Lead to Benign ProstaticHyperplasia viaThrombospondin-1Productionin Prostatic SmoothMuscleCells
Interleukin-18may Lead to Benign ProstaticHyperplasia viaThrombospondin-1Productionin Prostatic SmoothMuscleCells
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DOI：
10.1002/pros.22773
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发表时间：
2014-05-01
期刊：
影响因子：
2.8
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Hamakawa, Takashi;Sasaki, Shoichi;Kohri, Kenjiro
背景虽然炎症在良性前列腺增生（BPH）的发展中起着重要作用，但人们对这种发病机制的确切机制知之甚少。在这里，我们研究了炎症反应与 BPH 之间的关系。方法使用 cDNA 微阵列分析来识别最近建立的模拟人类 BPH 的大鼠模型中炎症相关基因表达的变化。为了研究分析中鉴定的基因，使用 BPH 模型组织、人前列腺组织和正常人前列腺培养细胞进行定量 (q)RT-PCR、蛋白质印迹、免疫染色和细胞增殖测定。 结果 在 cDNA 分析中鉴定的 31,100 个基因中，7 个炎症反应相关基因在大鼠 BPH 组织中的表达水平比正常大鼠前列腺组织高 2 倍以上。大鼠 BPH 组织中最常表达的促炎细胞因子 IL-18 的水平显着升高。在人类中，IL-18 定位于上皮和基质成分中，而其受体则强烈定位于平滑肌细胞中。此外，在人前列腺平滑肌细胞系 (PrSMC) 中，IL-18 会导致磷酸化 Akt 和血小板反应蛋白-1 (TSP-1) 水平呈剂量依赖性增加。 TSP-1 促进人前列腺基质细胞 (PrSC) 的增殖。结论IL-18 可能通过 Akt 磷酸化诱导前列腺平滑肌细胞产生 TSP-1，从而直接在 BPH 发病机制中发挥作用。前列腺 74:590-601, 2014。(c) 2014 Wiley periodicals, Inc.
BACKGROUNDAlthough inflammation plays an important role in the development of benign prostatic hyperplasia (BPH), little is known about the exact mechanism underlying this pathogenesis. Here, we investigated the relationship between the inflammatory reaction and BPH.METHODScDNA microarray analysis was used to identify changes in inflammation-related gene expression in a recently established rat model that mimics human BPH. To investigate the genes identified in the analysis, quantitative (q)RT-PCR, Western blotting, immunostaining, and a cell proliferation assay were conducted using BPH model tissues, human prostate tissues, and normal human prostate cultured cells.RESULTSOf the 31,100 genes identified in the cDNA analysis, seven inflammatory-response-related genes were expressed at a >2-fold higher level in rat BPH tissues than in normal rat prostate tissues. The levels of the most commonly expressed pro-inflammatory cytokine, IL-18, significantly increased in rat BPH tissues. In humans, IL-18 was localized in the epithelial and stromal components, while its receptor was strongly localized in smooth muscle cells. Furthermore, in human prostate smooth muscle cell line (PrSMC), IL-18 effected dose-dependent increases in the phosphorylated Akt and thrombospondin-1 (TSP-1) levels. TSP-1 promoted proliferation of the human prostate stromal cells (PrSC).CONCLUSIONSIL-18 may act directly in BPH pathogenesis by inducing TSP-1 production in prostatic smooth muscle cells via Akt phosphorylation. Prostate 74:590-601, 2014. (c) 2014 Wiley Periodicals, Inc.