title: Deletion of PPAR-γ in immune cells enhances susceptibility to antiglomerular basement membrane disease.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia- Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Cristen
authors.initials: C
authors.lastname: Chafin
authors.forename: Sarah
authors.initials: S
authors.lastname: Muse
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
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authors.lastname: Zhang
authors.forename: Liwu
authors.initials: L
authors.lastname: Li
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Reilly
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