Disruption of chemokine-glycosaminoglycan interactions protects the liver in the murine Concanavalin A-induced acute hepatits model
-
1
University of Louisville, Pathology & Laboratory Medicine, United States
-
2
University of Louisville, Medicine, United States
Autoimmune-mediated liver injury is responsible for the pathogenesis of immune-, viral- and drug-associated liver diseases, conditions that constitute a significant health problem worldwide. The purpose of this research was to investigate the therapeutic potential, in liver disease, of inhibitors that target chemokine interactions with glycosaminoglycans (GAGs). Because of the key role played by GAG-attached chemokines in the migration of leukocytes into inflamed tissues, we predicted that interference with the binding of chemokines to GAGs, would lead to reduced leukocyte infiltration and decreased liver damage in a Concanavalin-A (ConA)-induced model of acute hepatitis in mice. Administration of a synthetic peptide that interferes with the binding of chemokines to GAGs into ConA-treated mice resulted in significant protection against liver damage. Peptide-treated mice showed a substantial reduction in areas of hepatocyte necrosis upon histological examination, and had significantly lower serum levels of liver enzymes (ALT and AST) as well as hepatocyte apoptosis compared to mice that received only ConA. Immunofluorescent staining of liver slices showed that this protection was correlated with reduced hepatic levels of IFNg, IL-17 and TNFa as well as with significant reductions in the numbers of infiltrating T leukocytes and myeloid cells (both granulocytes and monocytes). Moreover, among the infiltrating T cells, peptide-treated animals showed reduced percentages of IFNg+-CD4+ and IFNg+-CD8+ cells. These results suggest that targeting chemokine/GAG interactions in vivo decreases the recruitment and activation of leukocytes and has potential as anti-inflammatory therapy in liver diseases.
Keywords:
Chemokines,
Glycosaminoglycans,
Hepatitis,
Leukocyte migration,
Interferon-gamma
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Fernandez-Botran
R,
Xie
Q,
Gobejishvili
L,
Zhang
J,
Joshi-Barve
S,
McClain
C and
Barve
S
(2013). Disruption of chemokine-glycosaminoglycan interactions protects the liver in the murine Concanavalin A-induced acute hepatits model.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00336
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
20 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Rafael Fernandez-Botran, University of Louisville, Pathology & Laboratory Medicine, Louisville, Kentucky, 40292, United States, rafael@louisville.edu