An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract.
An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract.
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DOI：
10.1038/ki.2013.395
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发表时间：
2014-05
影响因子：
19.6
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中科院分区：
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最近的研究强调了抗菌肽在保护尿路免受感染中的重要性。以前，我们已经表明，核糖核酸酶7（RNase 7）是一种有效的抗菌肽，对尿路病原菌具有广谱抗菌活性。下尿路的尿路上皮和肾脏的闰细胞产生RNase 7，但其抗微生物活性的调节尚未明确。在这里，我们表征的内源性抑制剂，核糖核酸酶抑制剂（RI），在尿路中的表达，并评估其对RNase 7的抗菌活性的影响。使用从未感染的人膀胱和肾组织中分离的RNA，定量实时PCR显示RNH1，编码RI的基因，在整个尿路中组成型表达。肾盂肾炎时，RNH1表达和RI肽产生显著减少。免疫组化显示RI主要分布于膀胱伞细胞和肾集合管闰细胞。体外实验表明，RI与RNase 7结合，并通过阻断其与尿路致病菌细胞壁结合的能力来抑制其抗菌活性。因此，这些结果证明了RI的一种新的免疫调节作用，并确定了一种独特的调节途径，可能会影响RNase 7如何维持尿路无菌。
Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7 but regulation of its antimicrobial activity has not been well defined. Here we characterize the expression of an endogenous inhibitor, ribonuclease inhibitor (RI), in the urinary tract and evaluate its effect on RNase 7’s antimicrobial activity. Using RNA isolated from non-infected human bladder and kidney tissue, quantitative real-time PCR showed that RNH1, the gene encoding RI, is constitutively expressed throughout the urinary tract. With pyelonephritis, RNH1 expression and RI peptide production significantly decrease. Immunostaining localized RI production to the umbrella cells of the bladder and intercalated cells of the renal collecting tubule. In vitro assays showed that RI bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. Thus, these results demonstrate a new immunomodulatory role for RI and identified a unique regulatory pathway that may affect how RNase 7 maintains urinary tract sterility.