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Preclinical evaluation of the urokinase receptor-derived peptide UPARANT as an anti-inflammatory drug

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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.

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Authors and Affiliations

  1. Department of Experimental Medicine, Università degli Studi della Campania, Naples, Italy

    Serena Boccella, Carmela Belardo, Mario De Rosa & Vito de Novellis

  2. Department of Pharmacy, University of Naples Federico II, Naples, Italy

    Elisabetta Panza & Angela Ianaro

  3. Department of Chemical Sciences, University of Naples Federico II, Naples, Italy

    Liliana Lista & Vincenzo Pavone

Authors
  1. Serena Boccella
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  2. Elisabetta Panza
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  3. Liliana Lista
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  4. Carmela Belardo
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  5. Angela Ianaro
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  6. Mario De Rosa
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  7. Vito de Novellis
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  8. Vincenzo Pavone
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Corresponding authors

Correspondence to Vito de Novellis or Vincenzo Pavone.

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Responsible Editor: Bernhard Gibbs.

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Boccella, S., Panza, E., Lista, L. et al. Preclinical evaluation of the urokinase receptor-derived peptide UPARANT as an anti-inflammatory drug. Inflamm. Res. 66, 701–709 (2017). https://doi.org/10.1007/s00011-017-1051-5

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  • DOI: https://doi.org/10.1007/s00011-017-1051-5

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