Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasia.
Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasia.
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DOI：
10.1002/pros.21081
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发表时间：
2010-04-01
期刊：
影响因子：
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通讯作者：
Pavlovich CP
中科院分区：
文献类型：
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作者：
Fujita K;Ewing CM;Getzenberg RH;Parsons JK;Isaacs WB;Pavlovich CP
慢性炎症常见于良性前列腺增生（BPH），前列腺组织常含有增加的炎性浸润，包括T细胞和巨噬细胞。细胞因子不仅是炎症的关键介质，而且可能在BPH的发生和发展中发挥重要作用。为了确定前列腺肥大可能与哪些细胞因子有关，我们采用人细胞因子抗体芯片和ELISA对离体前列腺的表达前列腺分泌物（EPS）进行了分析。使用前列腺上皮细胞（PrEC）和前列腺基质细胞（PrSC）进行ELISA、增殖和Western blot检测。单核细胞趋化蛋白-1 （MCP-1/CCL2）是大前列腺分泌物中升高最多的蛋白之一。发现PrSC分泌MCP-1；Western blotting结果显示，PrSC和PrEC均表达MCP-1受体CCR2， RT-PCR结果为CCR2b亚型。增殖实验表明，MCP-1能刺激PrEC的增殖，但不能刺激PrSC的增殖，并且一种特异性的MCP-1拮抗剂（RS102895）抑制了这种作用。来自PrSC的条件培养基也能刺激PrEC的增殖，这一作用被RS102895和一种中和性抗mcp -1单克隆抗体完全抑制。炎症因子白介素(IL)-1β、干扰素-γ和IL-2增强了PrEC和PrSC中MCP-1的分泌。此外，EPS中的MCP-1水平与相同分泌物中巨噬细胞标志物CD68的mRNA水平相关。细胞因子MCP-1起源于前列腺基质细胞，可能在前列腺肥大和BPH中发挥重要作用，是这些病理过程的候选生物标志物。
Chronic inflammation is commonly observed in benign prostate hyperplasia (BPH), and prostate tissue often contains increased inflammatory infiltrates, including T cells and macrophages. Cytokines are not only key mediators of inflammation but may also play important roles in the initiation and progression of BPH. In order to determine what cytokines might be involved in prostatic enlargement, expressed prostatic secretions (EPS) from ex vivo prostates were analyzed by human cytokine antibody microarray and ELISA. Prostate epithelial cells (PrEC) and prostate stromal cells (PrSC) were used for ELISA, proliferation, and Western blot assays. Monocyte chemotactic protein-1 (MCP-1/CCL2) was one of the most elevated proteins in secretions from large prostate glands. PrSC were found to secrete MCP-1; Western blotting showed that both PrSC and PrEC express the MCP-1 receptor CCR2 which by RT-PCR was the CCR2b isoform. Proliferation assays showed that MCP-1 stimulates the proliferation of PrEC, but not PrSC, and that a specific MCP-1 antagonist (RS102895) suppressed this effect. Conditioned medium from PrSC stimulated the proliferation of PrEC as well, an effect completely inhibited by both RS102895 and a neutralizing anti-MCP-1 monoclonal antibody. The inflammatory cytokines interleukin (IL)-1β, interferon-γ, and IL-2 enhanced the secretion of MCP-1 from PrEC and PrSC. In addition, MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 in the same secretions. The cytokine MCP-1, of apparent prostatic stromal cell origin, may play an important role in prostatic enlargement and BPH, and is a candidate biomarker for these pathologic processes.