Inhibition of COX-2 signaling favors E. coli during urinary tract infection.

IF 4.4 3区医学 Q2 IMMUNOLOGY

Journal of Inflammation-London Pub Date : 2023-09-11 DOI:10.1186/s12950-023-00356-9

Soumitra Mohanty, Ciska Lindelauf, John Kerr White, Andrea Scheffschick, Ewa Ehrenborg, Isak Demirel, Hanna Brauner, Annelie Brauner

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引用次数: 0

Abstract

Background: 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.

Results: 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.

Conclusions: Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.

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在尿路感染过程中抑制COX-2信号有利于大肠杆菌。

背景:为了避免抗生素的过度使用，非甾体类抗炎药(NSAIDs)通过抑制环氧化酶(COX)起作用，已被用于减轻疼痛，并作为非并发症尿路感染(uti)的替代治疗方法。然而，评估非甾体抗炎药与抗生素的临床研究报告了急性肾盂肾炎的风险增加。因此，我们假设COX抑制可能损害先天免疫反应，并导致无并发症尿路感染患者出现并发症。结果:我们在这里证明，特别是COX-2抑制导致抗菌肽银屑病蛋白和人β-防御素-2在人尿路上皮细胞中的表达降低。银屑病蛋白在中性粒细胞和巨噬细胞中的表达发生改变。COX-2抑制也影响炎性体介导的IL-1β表达，以应对尿路上皮大肠杆菌感染。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的条件培养基抑制大肠杆菌感染的尿上皮细胞未能激活巨噬细胞。结论:综上所述，我们的数据表明，在尿路感染期间，COX-2抑制对尿路上皮细胞有不利的先天免疫作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inflammation-London IMMUNOLOGY-

CiteScore

7.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Inflammation welcomes research submissions on all aspects of inflammation. The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings. Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.