Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease

Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease

Cristen Chafin2, Sarah Muse2, Raquel Hontecillas5, Josep Bassaganya-Riera5, David L Caudell2, Samuel K Shimp III4, M Nichole Rylander4, John Zhang6, Liwu Li3, Christopher M Reilly1,21Virginia College of Osteopathic Medicine, 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regi...

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Autores principales: Cristen Chafin, Sarah Muse, Raquel Hontecillas, et al
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2010
Materias:
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/2ea8a5718d5841099b072e7d963cfcaa
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spelling oai:doaj.org-article:2ea8a5718d5841099b072e7d963cfcaa2021-12-02T04:52:31ZDeletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease1178-7031https://doaj.org/article/2ea8a5718d5841099b072e7d963cfcaa2010-10-01T00:00:00Zhttp://www.dovepress.com/deletion-of-ppar-gamma-in-immune-cells-enhances-susceptibility-to-anti-a5563https://doaj.org/toc/1178-7031Cristen Chafin2, Sarah Muse2, Raquel Hontecillas5, Josep Bassaganya-Riera5, David L Caudell2, Samuel K Shimp III4, M Nichole Rylander4, John Zhang6, Liwu Li3, Christopher M Reilly1,21Virginia College of Osteopathic Medicine, 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 3Department of Biological Sciences, 4Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 5Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 6Medical University of SC, Charleston, SC, USAAbstract: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-γ gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM) mouse model. PPAR-γ+/+ and PPAR-γ-/- mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-γ+/+ and PPAR-γ-/- mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-γ-/- mice were significantly more severe compared with the PPAR-γ+/+ animals. We observed that the PPAR-γ-/- mice had decreased CD4+CD25+ regulatory T cells and an increased CD8+:CD4+ ratio as compared with the PPAR-γ+/+ mice, suggesting that PPAR-γ has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-γ-/- mice at two weeks as compared with the PPAR-γ+/+ animals. Taken together, these studies show that the lack of PPAR-γ expression enhances inflammatory renal disease in the anti-GBM antibody-induced glomerulonephritis mouse model and suggests targeting PPAR-γ may have therapeutic efficacy.Keywords: PPAR-γ, antiglomerular basement membrane disease  Cristen ChafinSarah MuseRaquel Hontecillaset alDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2010, Iss default, Pp 127-134 (2010)
institution DOAJ
collection DOAJ
language EN
topic Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Cristen Chafin
Sarah Muse
Raquel Hontecillas
et al
Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
description Cristen Chafin2, Sarah Muse2, Raquel Hontecillas5, Josep Bassaganya-Riera5, David L Caudell2, Samuel K Shimp III4, M Nichole Rylander4, John Zhang6, Liwu Li3, Christopher M Reilly1,21Virginia College of Osteopathic Medicine, 2Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 3Department of Biological Sciences, 4Department of Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 5Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; 6Medical University of SC, Charleston, SC, USAAbstract: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-γ gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM) mouse model. PPAR-γ+/+ and PPAR-γ-/- mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-γ+/+ and PPAR-γ-/- mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-γ-/- mice were significantly more severe compared with the PPAR-γ+/+ animals. We observed that the PPAR-γ-/- mice had decreased CD4+CD25+ regulatory T cells and an increased CD8+:CD4+ ratio as compared with the PPAR-γ+/+ mice, suggesting that PPAR-γ has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-γ-/- mice at two weeks as compared with the PPAR-γ+/+ animals. Taken together, these studies show that the lack of PPAR-γ expression enhances inflammatory renal disease in the anti-GBM antibody-induced glomerulonephritis mouse model and suggests targeting PPAR-γ may have therapeutic efficacy.Keywords: PPAR-γ, antiglomerular basement membrane disease 
format article
author Cristen Chafin
Sarah Muse
Raquel Hontecillas
et al
author_facet Cristen Chafin
Sarah Muse
Raquel Hontecillas
et al
author_sort Cristen Chafin
title Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
title_short Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
title_full Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
title_fullStr Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
title_full_unstemmed Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
title_sort deletion of ppar-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease
publisher Dove Medical Press
publishDate 2010
url https://doaj.org/article/2ea8a5718d5841099b072e7d963cfcaa
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AT raquelhontecillas deletionofpparampgammainimmunecellsenhancessusceptibilitytoantiglomerularbasementmembranedisease
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