Inflammasomes are important mediators of prostatic inflammation associated with BPH.
Inflammasomes are important mediators of prostatic inflammation associated with BPH.
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DOI：
10.1186/s12950-015-0082-3
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Tyagi P
中科院分区：
文献类型：
--
作者：
Kashyap M;Pore S;Wang Z;Gingrich J;Yoshimura N;Tyagi P
越来越多的证据支持炎症在良性前列腺增生症(BPH)中的作用，最近的一项研究报道了炎症体衍生细胞因子IL-18在BPH患者前列腺活检中的表达。在这里，我们研究了炎症体衍生的细胞因子的表达和核苷酸结合的寡聚结构域样受体与吡咯域蛋白1(NLRP)1在与BPH相关的大鼠前列腺炎症模型中的激活。3月龄雄性SD大鼠经前列腺前叶注射5%福尔马林或生理盐水(假手术)(50μL)诱导前列腺炎性反应。7d后，取前列腺和膀胱组织进行免疫印迹、免疫组织化学和Milliplex下游细胞因子分析。与假手术组相比，注射福尔马林后，前列腺液中白介素C、CXC和CC趋化因子的表达增加了2~15倍。前列腺癌组织中NLRP1炎症体成分和caspase-1的显著表达与IL-1前体和裂解型β显著升高(25.50 ± 1.16vs3.05 ± 0.65npg/mg蛋白)和IL-18(1646.15 ± 182.61 vs304.67 ± 103.95 pg/mg蛋白)。与前列腺组织相比，细胞因子在膀胱组织中的表达明显降低，且不涉及炎性小体的激活。NLRP1、Caspase-1及其下游细胞因子(IL-18和IL-1β)的表达显著上调，提示NLRP1炎性小体在该模型大鼠的前列腺组织中被组装并激活。总结人类BPH标本的研究结果表明，炎症小体可能使与BPH相关的炎症状态持续存在。进一步阐明这些途径可能会为BPH相关炎症提供创新的治疗靶点。
There is mounting evidence to support the role of inflammation in benign prostate hyperplasia (BPH), and a recent study reported expression of inflammasome derived cytokine IL-18 in prostate biopsy of BPH patients. Here we examined the expression of inflammasome-derived cytokines and activation of nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP) 1 inflammasome in a rat model of prostatic inflammation relevant to BPH. Prostatic inflammation was experimentally induced in three-month-old male Sprague–Dawley rats by intraprostatic injection (50 μL) of either 5 % formalin or saline (sham) into the ventral lobes of prostate. 7 days later, prostate and bladder tissue was harvested for analysis of inflammasome by Western blot, immunohistochemistry and downstream cytokine production by Milliplex. Expression of interleukins, CXC and CC chemokines were elevated 2-15 fold in formalin injected prostate relative to sham. Significant expression of NLRP1 inflammasome components and caspase-1 in prostate were associated with significant elevation of pro and cleaved forms of IL-1β (25.50 ± 1.16 vs 3.05 ± 0.65 pg/mg of protein) and IL-18 (1646.15 ± 182.61 vs 304.67 ± 103.95 pg/mg of protein). Relative to prostate tissue, the cytokine expression in bladder tissue was much lower and did not involve inflammasome activation. Significant upregulation of NLRP1, caspase-1 and downstream cytokines (IL-18 and IL-1β) suggests that a NLRP1 inflammasome is assembled and activated in prostate tissue of this rat model. Recapitulation of findings from human BPH specimens suggests that the inflammasome may perpetuate the inflammatory state associated with BPH. Further clarification of these pathways may offer innovative therapeutic targets for BPH-related inflammation.
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影响因子：
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作者：
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