Ceramides: a potential therapeutic target in pulmonary emphysema

Research

Jeroen Tibboel¹³, Irwin Reiss³, Johan C de Jongste³ and Martin Post^12*

• *Corresponding author: Martin Post martin.post@sickkids.ca

Author Affiliations

¹Physiology and Experimental Medicine Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

²Department of Laboratory Medicine and Pathobiology, University Of Toronto, Toronto, Canada

³Department of Pediatrics, Erasmus University Medical Center – Sophia Children’s Hospital, Rotterdam, the Netherlands

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Respiratory Research 2013, 14:96 doi:10.1186/1465-9921-14-96

The electronic version of this article is the complete one and can be found online at:http://respiratory-research.com/content/14/1/96

Received:	24 June 2013
Accepted:	25 September 2013
Published:	1 October 2013

© 2013 Tibboel et al.; licensee BioMed Central Ltd. 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The aim of this manuscript was to characterize airway ceramide profiles in a rodent model of elastase-induced emphysema and to examine the effect of pharmacological intervention directed towards ceramide metabolism.

Methods

Adult mice were anesthetized and treated with an intratracheal instillation of elastase. Lung function was measured, broncho-alveolar lavage fluid collected and histological and morphometrical analysis of lung tissue performed within 3 weeks after elastase injection, with and without sphingomyelinase inhibitors or serine palmitoyltransferase inhibitor. Ceramides in broncho-alveolar lavage (BAL) fluid were quantified by tandem mass spectrometry.

Results

BAL fluid showed a transient increase in total protein and IgM, and activated macrophages and neutrophils. Ceramides were transiently upregulated at day 2 after elastase treatment. Histology showed persistent patchy alveolar destruction at day 2 after elastase installation. Acid and neutral sphingomyelinase inhibitors had no effect on BAL ceramide levels, lung function or histology. Addition of a serine palmitoyltransferase inhibitor ameliorated lung function changes and reduced ceramides in BAL.

Conclusions

Ceramides were increased during the acute inflammatory phase of elastase-induced lung injury. Since addition of a serine palmitoyltransferase inhibitor diminished the rise in ceramides and ameliorated lung function, ceramides likely contributed to the early phase of alveolar destruction and are a potential therapeutic target in the elastase model of lung emphysema.

Keywords: 

Elastase; Sphingolipids; Ceramide; Lung function