School of Pharmacy, Department of Pharmacology, University of Mississippi, Oxford, MS, USA.
J Inflamm (Lond). 2009 Jan 27;6:3. doi: 10.1186/1476-9255-6-3.
Prolylcarboxypeptidase (Prcp) gene, along with altered PRCP and kallikrein levels, have been implicated in inflammation pathogenesis. PRCP regulates angiotensin 1-7 (Ang 1-7) - and bradykinin (BK) - stimulated nitric oxide production in endothelial cells. The mechanism through which kallikrein expression is altered during infection is not fully understood. Investigations were performed to determine the association between PRCP and kallikrein levels as a function of the upregulation of PRCP expression and the link between PRCP and inflammation risk in lipopolysaccharide (LPS)-induced endothelium activation.
The Prcp transcript expression in LPS-induced human umbilical vein endothelial cells (HUVEC) activation was determined by RT-PCR for mRNA. PRCP-dependent kallikrein pathway was determined either by Enzyme Linked ImmunoSorbent Assay (ELISA) or by biochemical assay.
We report that PRCP is critical to the maintenance of the endothelial cells, and its upregulation contributes to the risk of developing inflammation. Significant elevation in kallikrein was seen on LPS-treated HUVECs. The conversion of PK to kallikrein was blocked by the inhibitor of PRCP, suggesting that PRCP might be a risk factor for inflammation.
The increased PRCP lead to a sustained production of bradykinin in endothelium following LPS treatment. This amplification may be an additional mechanism whereby PRCP promotes a sustained inflammatory response. A better appreciation of the role of PRCP in endothelium may contribute to a better understanding of inflammatory vascular disorders and to the development of a novel treatment.
脯氨酰羧肽酶（Prcp）基因以及改变的 Prcp 和激肽释放酶水平与炎症发病机制有关。Prcp 调节血管紧张素 1-7（Ang 1-7）和缓激肽（BK）刺激内皮细胞中一氧化氮的产生。在感染过程中激肽释放酶表达改变的机制尚不完全清楚。进行了研究以确定 PRCP 和激肽释放酶水平与 PRCP 表达上调的相关性，以及 PRCP 与脂多糖（LPS）诱导的内皮细胞激活中炎症风险之间的联系。
通过 RT-PCR 确定 LPS 诱导的人脐静脉内皮细胞（HUVEC）激活中 Prcp 转录物的表达。通过酶联免疫吸附测定（ELISA）或生化测定确定 PRCP 依赖性激肽释放酶途径。
我们报告 PRCP 对内皮细胞的维持至关重要，其上调会增加炎症的风险。在 LPS 处理的 HUVEC 上观察到激肽释放酶显著升高。PRCP 抑制剂阻断 PK 向激肽释放酶的转化，表明 PRCP 可能是炎症的危险因素。
LPS 处理后，PRCP 的增加导致内皮细胞中缓激肽的持续产生。这种放大可能是 PRCP 促进持续炎症反应的另一种机制。更好地了解 PRCP 在血管内皮细胞中的作用可能有助于更好地理解炎症性血管疾病，并开发新的治疗方法。
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