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Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration

There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into tar...

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Autores principales: Vogel, Megan E., Zucker, Stephen D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768809/
https://www.ncbi.nlm.nih.gov/pubmed/26925435
http://dx.doi.org/10.14800/ics.1178
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author Vogel, Megan E.
Zucker, Stephen D.
author_facet Vogel, Megan E.
Zucker, Stephen D.
author_sort Vogel, Megan E.
collection PubMed
description There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by in vitro experiments showing that bilirubin blocks the VCAM-1-dependent movement of Jurkat cells across human endothelial cell monolayers. Taken together, our findings support that bilirubin ameliorates DSS-induced colitis and disrupts the physiological trafficking of leukocytes to the intestine by preventing transmigration across the vascular endothelium, potentially through the inhibition VCAM-1-mediated signaling. Our findings raise the possibility that bilirubin functions as an endogenous regulator of inflammatory responses.
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spelling pubmed-47688092016-02-26 Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration Vogel, Megan E. Zucker, Stephen D. Inflamm Cell Signal Article There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by in vitro experiments showing that bilirubin blocks the VCAM-1-dependent movement of Jurkat cells across human endothelial cell monolayers. Taken together, our findings support that bilirubin ameliorates DSS-induced colitis and disrupts the physiological trafficking of leukocytes to the intestine by preventing transmigration across the vascular endothelium, potentially through the inhibition VCAM-1-mediated signaling. Our findings raise the possibility that bilirubin functions as an endogenous regulator of inflammatory responses. 2016-02-15 2016 /pmc/articles/PMC4768809/ /pubmed/26925435 http://dx.doi.org/10.14800/ics.1178 Text en http://creativecommons.org/licenses/by-nc/4.0/ Licensed under a Creative Commons Attribution 4.0 International License which allows users including authors of articles to copy and redistribute the material in any medium or format, in addition to remix, transform, and build upon the material for any purpose, even commercially, as long as the author and original source are properly cited or credited.
spellingShingle Article
Vogel, Megan E.
Zucker, Stephen D.
Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
title Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
title_full Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
title_fullStr Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
title_full_unstemmed Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
title_short Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
title_sort bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768809/
https://www.ncbi.nlm.nih.gov/pubmed/26925435
http://dx.doi.org/10.14800/ics.1178
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