The inflammatory microenvironment of the aging prostate facilitates cellular proliferation and hypertrophy
The inflammatory microenvironment of the aging prostate facilitates cellular proliferation and hypertrophy
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DOI：
10.1016/j.cyto.2008.05.012
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发表时间：
2008-08-01
期刊：
影响因子：
3.8
通讯作者：
Macoska, J. A.
中科院分区：
文献类型：
--
作者：
Begley, L. A.;Kasina, S.;Macoska, J. A.
良性前列腺肥大（BPH，也称为良性前列腺增生或良性前列腺肿大）是与男性衰老相关的最常见的良性增殖性病症之一，其病理特征在于前列腺中成纤维细胞/肌成纤维细胞和上皮细胞类型的增殖。我们实验室之前的研究表明，CXC型趋化因子CXCL 5和CXCL 12由衰老的前列腺基质分泌，并促进前列腺上皮细胞的增殖和转录反应。利用基于阵列的基因表达谱分析和定量逆转录聚合酶链反应，我们发现衰老前列腺间质的转录组以编码分泌的炎症介质（包括分泌的CXC型趋化因子）的几个基因的上调为特征（CXCL 1、CXCL 2、CXCL 5、CXCL 6、CXCL 12）、白细胞介素（IL 11、IL 33）和具有细胞因子同源性的转录物（CYTL 1）。在蛋白质水平，ELISA实验表明，CXCL 1，CXCL 5和CXCL 6分泌的原代前列腺基质成纤维细胞从老化的前列腺基质。剂量反应测定证实，与CXCL 5和CXCL 12一样，CXCL 1和CXCL 6促进前列腺基质成纤维细胞和上皮细胞的低水平增殖反应。总之，这些数据表明，炎症介质是由前列腺基质分泌的老化，这些介质的水平足以促进低水平的增加，上皮和基质成纤维细胞类型的增殖率。此外，这些过程可以解释上皮细胞和成纤维细胞/成肌纤维细胞类型的低水平但累积的增殖，其特征在于良性前列腺肥大的衰老相关发展。(c)2008爱思唯尔有限公司保留所有权利。
Benign Prostatic Hypertrophy (BPH, also known as benign prostatic hyperplasia or benign prostatic enlargement), is one of the most common benign proliferative conditions associated with aging in men and is pathologically characterized by the proliferation of fibroblast/myofibroblast and epithelial cell types in the prostate. Previous studies from our laboratory have shown that the CXC-type chemokines, CXCL5 and CXCL12, are secreted by aging prostate stroma and promote both proliferative and transcriptional responses from prostate epithelial cells. Using array-based gene expression profiling and quantitative reverse-transcriptase polymerase chain reaction, we now show that the transcriptome of the aging prostate stroma is characterized by the up-regulation of several genes that encode secreted inflammatory mediators, including secreted CXC-type chemokines (CXCL1, CXCL2, CXCL5, CXCL6, CXCL12), interleukins (IL11, IL33), and transcripts with cytokine homology (CYTL1). At the protein level, ELISA experiments demonstrated that CXCL1, CXCL5, and CXCL6 were secreted by primary prostate stromal fibroblasts explanted from aging prostate stroma. Dose-response assays confirmed that, like CXCL5 and CXCL12, CXCL1 and CXCL6 promote low-level proliferative responses from both prostate stromal fibroblasts and epithelial cells. Taken together, these data suggest that inflammatory mediators are secreted by prostatic stroma consequent to aging, that the levels of these mediators are sufficient to promote low-level increases in the proliferative rate of both epithelial and stromal fibroblast cell types. Moreover, these processes may account for the low-level, but cumulative, proliferation of both epithelial and fibroblastic/myofibroblastic cell types that characterizes the aging-associated development of benign prostatic hypertophy. (c) 2008 Elsevier Ltd. All rights reserved.