Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by...

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Main Authors: Talero Elena, Di Paola Rosanna, Mazzon Emanuela, Emanuela Esposito, Motilva Virginia, Cuzzocrea Salvatore
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2012/717851
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author Talero Elena
Di Paola Rosanna
Mazzon Emanuela
Emanuela Esposito
Motilva Virginia
Cuzzocrea Salvatore
author_facet Talero Elena
Di Paola Rosanna
Mazzon Emanuela
Emanuela Esposito
Motilva Virginia
Cuzzocrea Salvatore
author_sort Talero Elena
collection DOAJ
description Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors.
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spelling doaj-art-a7925af382634d9b886f5738747dd26f2025-02-03T01:02:59ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/717851717851Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in MiceTalero Elena0Di Paola Rosanna1Mazzon Emanuela2Emanuela Esposito3Motilva Virginia4Cuzzocrea Salvatore5Department of Pharmacology, School of Pharmacy, University of Seville, 41012 Seville, SpainDepartment of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98100 Messina, ItalyDepartment of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98100 Messina, ItalyDepartment of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98100 Messina, ItalyDepartment of Pharmacology, School of Pharmacy, University of Seville, 41012 Seville, SpainDepartment of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98100 Messina, ItalyAdrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors.http://dx.doi.org/10.1155/2012/717851
spellingShingle Talero Elena
Di Paola Rosanna
Mazzon Emanuela
Emanuela Esposito
Motilva Virginia
Cuzzocrea Salvatore
Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice
Mediators of Inflammation
title Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice
title_full Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice
title_fullStr Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice
title_full_unstemmed Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice
title_short Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice
title_sort anti inflammatory effects of adrenomedullin on acute lung injury induced by carrageenan in mice
url http://dx.doi.org/10.1155/2012/717851
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