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Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells

Inflammatory bowel disease (IBD) is a highly prevalent intestinal disorder for which no cure exists. Currently, the standard first-line treatment of IBD consists of systemic glucocorticoid (GC) application, even though therapy can be complicated by unresponsiveness or adverse effects. In view of the...

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Autores principales: Meers, Garrit K., Bohnenberger, Hanibal, Reichardt, Holger M., Lühder, Fred, Reichardt, Sybille D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764312/
https://www.ncbi.nlm.nih.gov/pubmed/29324769
http://dx.doi.org/10.1371/journal.pone.0190846
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author Meers, Garrit K.
Bohnenberger, Hanibal
Reichardt, Holger M.
Lühder, Fred
Reichardt, Sybille D.
author_facet Meers, Garrit K.
Bohnenberger, Hanibal
Reichardt, Holger M.
Lühder, Fred
Reichardt, Sybille D.
author_sort Meers, Garrit K.
collection PubMed
description Inflammatory bowel disease (IBD) is a highly prevalent intestinal disorder for which no cure exists. Currently, the standard first-line treatment of IBD consists of systemic glucocorticoid (GC) application, even though therapy can be complicated by unresponsiveness or adverse effects. In view of the importance of macrophages and neutrophils for the pathogenesis of IBD we set out to define the relevance of these cell types as targets of GC using the mouse model of DSS-induced colitis. We found that the disease did not resolve in GR(lysM) mice lacking the GC receptor (GR) in myeloid cells after removal of the chemical insult. While clinical symptoms and tissue damage in the colon ameliorated again in GR(flox) mice, the disease further aggravated in GR(lysM) littermates. The observed difference coincided with an increased abundance of macrophages in inflammatory infiltrates in the colon of mutant mice whereas neutrophil and T cell numbers were similar. Concomitantly, systemic IL-6 secretion and mRNA levels of pro-inflammatory cytokines in the colon were elevated in GR(lysM) mice and gene expression of scavenger receptors and IL-10 was diminished. Taken together, our results reveal an important role of myeloid cells as targets of GC in DSS-induced colitis and probably in IBD in humans as well.
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spelling pubmed-57643122018-01-23 Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells Meers, Garrit K. Bohnenberger, Hanibal Reichardt, Holger M. Lühder, Fred Reichardt, Sybille D. PLoS One Research Article Inflammatory bowel disease (IBD) is a highly prevalent intestinal disorder for which no cure exists. Currently, the standard first-line treatment of IBD consists of systemic glucocorticoid (GC) application, even though therapy can be complicated by unresponsiveness or adverse effects. In view of the importance of macrophages and neutrophils for the pathogenesis of IBD we set out to define the relevance of these cell types as targets of GC using the mouse model of DSS-induced colitis. We found that the disease did not resolve in GR(lysM) mice lacking the GC receptor (GR) in myeloid cells after removal of the chemical insult. While clinical symptoms and tissue damage in the colon ameliorated again in GR(flox) mice, the disease further aggravated in GR(lysM) littermates. The observed difference coincided with an increased abundance of macrophages in inflammatory infiltrates in the colon of mutant mice whereas neutrophil and T cell numbers were similar. Concomitantly, systemic IL-6 secretion and mRNA levels of pro-inflammatory cytokines in the colon were elevated in GR(lysM) mice and gene expression of scavenger receptors and IL-10 was diminished. Taken together, our results reveal an important role of myeloid cells as targets of GC in DSS-induced colitis and probably in IBD in humans as well. Public Library of Science 2018-01-11 /pmc/articles/PMC5764312/ /pubmed/29324769 http://dx.doi.org/10.1371/journal.pone.0190846 Text en © 2018 Meers et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Meers, Garrit K.
Bohnenberger, Hanibal
Reichardt, Holger M.
Lühder, Fred
Reichardt, Sybille D.
Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
title Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
title_full Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
title_fullStr Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
title_full_unstemmed Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
title_short Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
title_sort impaired resolution of dss-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764312/
https://www.ncbi.nlm.nih.gov/pubmed/29324769
http://dx.doi.org/10.1371/journal.pone.0190846
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