Department of Biological Sciences, University of Texas at Dallas, Richardson, TX, USA.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Life Sci Alliance. 2021 May 6;4(7). doi: 10.26508/lsa.202000948. Print 2021 Jul.
Urinary tract infection (UTI) is one of the most common adult bacterial infections and exhibits high recurrence rates, especially in postmenopausal women. Studies in mouse models suggest that cyclooxygenase-2 (COX-2)-mediated inflammation sensitizes the bladder to recurrent UTI (rUTI). However, COX-2-mediated inflammation has not been robustly studied in human rUTI. We used human cohorts to assess urothelial COX-2 production and evaluate its product, PGE, as a biomarker for rUTI in postmenopausal women. We found that the percentage of COX-2-positive cells was elevated in inflamed versus uninflamed bladder regions. We analyzed the performance of urinary PGE as a biomarker for rUTI in a controlled cohort of 92 postmenopausal women and PGE consistently outperformed all other tested clinical variables as a predictor of rUTI status. Furthermore, time-to-relapse analysis indicated that the risk of rUTI relapse was 3.6 times higher in women with above median urinary PGE levels than with below median levels. Taken together, these data suggest that urinary PGE may be a clinically useful diagnostic and prognostic biomarker for rUTI in postmenopausal women.
尿路感染（UTI）是最常见的成人细菌性感染之一，其复发率很高，尤其是在绝经后妇女中。小鼠模型研究表明，环氧合酶-2（COX-2）介导的炎症会使膀胱对复发性 UTI（rUTI）敏感。然而，COX-2 介导的炎症在人类 rUTI 中尚未得到充分研究。我们使用人类队列评估尿路上皮 COX-2 的产生，并评估其产物 PGE 作为绝经后妇女 rUTI 的生物标志物。我们发现，与非炎症区域相比，炎症膀胱区域的 COX-2 阳性细胞百分比升高。我们分析了尿 PGE 作为 92 名绝经后妇女对照队列中 rUTI 生物标志物的性能，PGE 始终优于其他所有测试的临床变量作为 rUTI 状态的预测因子。此外，复发时间分析表明，尿 PGE 水平高于中位数的妇女 rUTI 复发的风险比低于中位数的妇女高 3.6 倍。综上所述，这些数据表明，尿 PGE 可能是绝经后妇女 rUTI 的一种有临床应用价值的诊断和预后生物标志物。
