Boccella Serena, Panza Elisabetta, Lista Liliana, Belardo Carmela, Ianaro Angela, De Rosa Mario, de Novellis Vito, Pavone Vincenzo
Department of Experimental Medicine, Università degli Studi della Campania, Naples, Italy.
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Inflamm Res. 2017 Aug;66(8):701-709. doi: 10.1007/s00011-017-1051-5. Epub 2017 Apr 29.
Inflammation plays a key role in the pathogenesis of several chronic diseases. The urokinase plasminogen activator receptor (uPAR) exerts a plethora of functions in both physiological and pathological processes, including inflammation.
In this study, we evaluated the anti-inflammatory effect of a novel peptide ligand of uPAR, UPARANT, in different animal models of inflammation.
Rats and mice were divided in different groups (n = 5) for single or repeated administration of vehicle (9% DMSO in 0.9% NaCl), UPARANT (6, 12 and 24 mg/kg) or dexamethasone (2 mg/kg). Animals were subjected to carrageenan-induced paw oedema or zymosan-induced peritonitis.
UPARANT effects were tested on: (1) the carrageenan-induced paw oedema volume, (2) the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the nitrite/nitrate (NOx) levels in the paw exudates, (3) cells recruitment into the peritoneal cavity after zymosan injection and (4) NOx levels in the peritoneal lavage.
UPARANT (12 and 24 mg/kg) reduced inflammation in both experimental paradigms. Analysis of pro-inflammatory enzymes revealed that administration of UPARANT reduced iNOS, COX2 and NO over-production.
Our study provides a solid evidence that UPARANT reduces the severity of inflammation in diverse animal models, thus representing a novel anti-inflammatory drug with potential advantages with respect to the typical steroidal agents.
炎症在多种慢性疾病的发病机制中起关键作用。尿激酶型纤溶酶原激活物受体（uPAR）在包括炎症在内的生理和病理过程中发挥多种功能。
在本研究中，我们评估了一种新型uPAR肽配体UPARANT在不同炎症动物模型中的抗炎作用。
将大鼠和小鼠分为不同组（n = 5），分别单次或重复给予溶媒（0.9%氯化钠中的9%二甲基亚砜）、UPARANT（6、12和24 mg/kg）或地塞米松（2 mg/kg）。对动物进行角叉菜胶诱导的爪肿胀或酵母聚糖诱导的腹膜炎实验。
检测UPARANT对以下指标的影响：（1）角叉菜胶诱导的爪肿胀体积；（2）爪渗出液中诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的表达及亚硝酸盐/硝酸盐（NOx）水平；（3）酵母聚糖注射后腹腔内细胞募集情况；（4）腹腔灌洗液中的NOx水平。
UPARANT（12和24 mg/kg）在两种实验模型中均减轻了炎症。对促炎酶的分析显示，给予UPARANT可减少iNOS、COX2的产生及NO的过量生成。
我们的研究提供了确凿证据，表明UPARANT可减轻多种动物模型中的炎症严重程度，因此是一种新型抗炎药物，相对于典型的甾体类药物具有潜在优势。
