Suppression of Autoimmunity and Renal Disease in Pristane-Induced Lupus by Myeloperoxidase

Arthritis & Rheumatology
Dragana OdobasicS R Holdsworth

Abstract

Myeloperoxidase (MPO) locally contributes to organ damage in various chronic inflammatory conditions by generating reactive intermediates. The contribution of MPO in the development of experimental lupus is unknown. The aim of this study was to define the role of MPO in murine lupus nephritis (LN). LN was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO(-/-) ) mice by intraperitoneal injection of pristane. Autoimmunity and glomerulonephritis were assessed 20 and 40 weeks after pristane administration. Cell apoptosis, leukocyte accumulation, and cytokine levels in the peritoneal cavity of WT and MPO(-/-) mice were assessed 3 or 6 days after pristane injection. MPO(-/-) mice developed more severe nephritis than did WT mice 20 and 40 weeks after pristane injection, despite having reduced glomerular deposition of antibody and complement and diminished levels of markers of oxidative stress (oxidized DNA and glutathione sulfonamide). Enhancement of renal disease in MPO-deficient mice correlated with increased accumulation of CD4+ T cells and macrophages in glomeruli, which, in turn, was associated with augmented generation of CD4+ T cell responses and increased activation and migration of dendritic cells in secondary lymphoid ...Continue Reading

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Citations

Mar 22, 2016·Oxidative Medicine and Cellular Longevity·Silvie KremserovaLukas Kubala
Feb 24, 2016·Journal of Immunology Research·Dragana OdobasicStephen R Holdsworth
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Jun 5, 2019·Kidney & Blood Pressure Research·Xiaoyan LiWeiqiang Lin

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