Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate
Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate
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DOI：
10.1002/pros.10238
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发表时间：
2003-08-01
期刊：
影响因子：
2.8
通讯作者：
Marberger, MJ
中科院分区：
文献类型：
--
作者：
Steiner, GE;Newman, ME;Marberger, MJ
导言和说明。为了研究除IL-15以外的前列腺炎症相关因素，我们筛选了前列腺细胞和组织中IL-17和IL-17受体的表达。对正常前列腺（n = 1）、BPH（n = 19）和癌（Cap，n = 12）标本进行IL-17、IL-17受体、CD 45、IL-6和IL-8 mRNA表达筛查。通过RT-PCR和ELISA分析癌细胞系DU 145、PC 3、LNCaP和BPH-上皮（EC）、基质细胞（SC）制备物和BPH-T-细胞系的IL-17产生。使用实时PCR和/或ELISA分析IL-17对IL-6、IL-8、TGF-β 1和成纤维细胞生长因子（FGF-2）mRNA表达和/或SC释放的影响。用免疫组织化学定位IL-17和IL-17受体。在正常前列腺中，IL-17表达非常弱，仅限于淋巴细胞。在79%的BPH和58%的CaP标本中，IL-17 mRNA和蛋白表达增加。活化的BPH-T细胞和BPH-EC在一定程度上可显示IL-17 mRNA表达。IL-17受体的表达是普遍存在的。仅对活化的BPH-T细胞显示IL-17的释放。IL-17刺激前列腺BPH-SC表达IL-6（13倍）和IL-8（26倍），但BPH组织中IL-17 mRNA的表达量与IL-6和IL-8 mRNA的表达量无相关性。CaP组织中IL-6和IL-8 mRNA表达量之间存在显著相关性。活化的BPH-T细胞大量表达IL-17。BPH组织中IL-17的增加与IL-15水平的升高密切相关，IL-15是一种具有T细胞生长因子特性的促炎细胞因子。通过证实IL-17显著上调前列腺SC的IL-6和IL-8产生，提示了病理条件下IL-17表达增加的临床相关性。
INTRODUCTION AND OBJECTIVES. To investigate factors involved in inflammation of the prostate besides IL-15, we screened prostatic cells and tissues for IL-17 and IL-17 receptor expression.METHODS. Normal prostate (n = 1), BPH (n = 19), and carcinoma (Cap, n = 12) specimens were screened for IL-17, IL-17 receptor, CD45, IL-6, and IL-8 mRNA expression. The carcinoma cell lines DU145, PC3, LNCaP, and BPH-epithelial (EC), stromal cell (SC) preparations, and BPH-T-cell lines were analyzed for IL-17 production by RT-PCR and ELISA. The effect of IL-17 on IL-6, IL-8, TGF-beta1, and fibroblast growth factor (FGF-2) mRNA expression and/or release of SC was analyzed using real-time PCR and/or ELISA. Immunohistochemistry was used to localize both IL-17 and IL-17 receptor.RESULTS. In the normal prostate, IL-17 expression was very weak and restricted to lymphocytes. In 79% of BPH and 58% of CaP specimens, IL-17 mRNA and protein expression was increased. IL-17 mRNA expression could be shown for activated BPH-T-cells and to some extend for BPH-EC. Expression of IL-17 receptor was ubiquitous. Release of IL-17 was shown only for activated BPH-T-cells. IL-17 stimulated expression of IL-6 (13-fold) and IL-8 (26-fold) by prostatic BPH-SC. In situ, however, the amount of IL-17mRNA in BPH-tissue did not correlate with the amount of IL-6 and IL-8 mRNA. In CaP tissue, significant correlation was found only between the amount of IL-6 and IL-8 mRNA.CONCLUSIONS. Activated BPH-T-cells abundantly express IL-17. The increase of IL-17 in BPH-tissues goes hand in hand with elevated levels of IL-15, a pro-inflammatory cytokine with T-cell growth factor properties. A clinical relevance of increased IL-17 expression under pathological conditions is suggested by the demonstration of significant upregulation of IL-6 and IL-8 production of prostatic SC by IL-17.