Logadottir Yr, Delbro Dick, Fall Magnus, Gjertsson Inger, Jirholt Pernilla, Lindholm Catharina, Peeker Ralph
Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
J Urol. 2014 Nov;192(5):1564-8. doi: 10.1016/j.juro.2014.04.099. Epub 2014 May 9.
Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls.
Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count.
IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C.
Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications.
与非Hunner膀胱疼痛综合征患者及健康对照者中无法检测到的一氧化氮相比，3C型膀胱疼痛综合征患者膀胱壁一氧化氮生成增加。然而，一氧化氮生成增加的潜在机制在很大程度上尚不清楚。我们比较了3C型膀胱疼痛综合征/间质性膀胱炎患者与无痛对照者中一组特定细胞因子的mRNA表达。
分析了7例3C型膀胱疼痛综合征患者和6名健康受试者的冷杯活检组织。通过实时聚合酶链反应估计白细胞介素-4、6、10和17A、诱导型一氧化氮合酶、肿瘤坏死因子-α、转化生长因子-β和干扰素-γ的mRNA表达。通过免疫组织化学测定白细胞介素-17蛋白表达。用类胰蛋白酶标记肥大细胞以评估细胞外观和计数。
与健康对照者相比，3C型膀胱疼痛综合征患者中白细胞介素-6、10和17A以及诱导型一氧化氮合酶的mRNA水平以及浸润膀胱黏膜的肥大细胞数量显著增加。患者和对照者中肿瘤坏死因子-α、转化生长因子-β和干扰素-γ的mRNA水平相似。3C型膀胱疼痛综合征患者中白细胞介素-17A在蛋白水平的表达上调，并定位于炎症细胞和尿路上皮。
膀胱疼痛综合征/间质性膀胱炎患者中白细胞介素-17A、10和6以及诱导型一氧化氮合酶的mRNA水平升高。白细胞介素-17A可能在炎症过程中起重要作用。据我们所知，白细胞介素-17A的增加是一项可能具有新治疗意义的新发现。
