Mohanty Soumitra, Lindelauf Ciska, White John Kerr, Scheffschick Andrea, Ehrenborg Ewa, Demirel Isak, Brauner Hanna, Brauner Annelie
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
J Inflamm (Lond). 2023 Sep 11;20(1):30. doi: 10.1186/s12950-023-00356-9.
To avoid the overuse of antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), acting via cyclooxygenase (COX) inhibition, have been used to reduce pain and as an alternative treatment for uncomplicated urinary tract infections (UTIs). However, clinical studies evaluating NSAIDs versus antibiotics have reported an increased risk of acute pyelonephritis. Therefore, we hypothesized that COX inhibition could compromise the innate immune response and contribute to complications in patients with uncomplicated UTI.
We here demonstrate that in particular COX-2 inhibition led to decreased expression of the antimicrobial peptides psoriasin and human β-defensin-2 in human uroepithelial cells. Psoriasin expression was altered in neutrophils and macrophages. COX-2 inhibition also had impact on the inflammasome mediated IL-1β expression in response to uroepithelial E. coli infection. Further, COX-2 inhibition downregulated free radicals and the epithelial barrier protein claudin 1, favoring infectivity. In addition, conditioned media from COX-2 inhibited uroepithelial cells infected with E. coli failed to activate macrophages.
Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.
为避免抗生素的过度使用，通过抑制环氧化酶（COX）发挥作用的非甾体抗炎药（NSAIDs）已被用于减轻疼痛，并作为单纯性尿路感染（UTIs）的替代治疗方法。然而，评估NSAIDs与抗生素疗效的临床研究报告称，急性肾盂肾炎的风险有所增加。因此，我们推测COX抑制可能会损害先天性免疫反应，并导致单纯性UTI患者出现并发症。
我们在此证明，特别是COX-2抑制导致人尿道上皮细胞中抗菌肽银屑素和人β-防御素-2的表达降低。中性粒细胞和巨噬细胞中的银屑素表达发生了改变。COX-2抑制对炎症小体介导的IL-1β表达也有影响，这是对尿道上皮大肠杆菌感染的反应。此外，COX-2抑制下调自由基和上皮屏障蛋白claudin 1，有利于感染性。此外，来自COX-2抑制的尿道上皮细胞感染大肠杆菌后的条件培养基未能激活巨噬细胞。
综上所述，我们的数据表明COX-2抑制在UTI期间对尿道上皮细胞具有不良的先天性免疫作用。
