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- Title
Preclinical evaluation of the urokinase receptor-derived peptide UPARANT as an anti-inflammatory drug.
- Authors
Boccella, Serena; Panza, Elisabetta; Lista, Liliana; Belardo, Carmela; Ianaro, Angela; Rosa, Mario; Novellis, Vito; Pavone, Vincenzo
- Abstract
Background: 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. Objective and design: In this study, we evaluated the anti-inflammatory effect of a novel peptide ligand of uPAR, UPARANT, in different animal models of inflammation. Subjects and treatment: 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. Methods: 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. Results: 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. Conclusions: 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.
- Subjects
INFLAMMATION; CHRONIC diseases; PERITONEAL dialysis; NITRIC-oxide synthases; EDEMA
- Publication
Inflammation Research, 2017, Vol 66, Issue 8, p701
- ISSN
1023-3830
- Publication type
Article
- DOI
10.1007/s00011-017-1051-5