S100A8/A9 (calprotectin) is critical for development of glomerulonephritis and promotes inflammatory leukocyte-renal cell interactions

The American Journal of Pathology
Ruth J PepperAlan D Salama

Abstract

Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9(-/-)), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow-derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14(-/-) cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow-derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14...Continue Reading

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Citations

May 21, 2016·Frontiers in Immunology·Michelle A SugimotoMauro M Teixeira
Oct 25, 2016·Autoimmunity Reviews·Francesca BruniniCharles D Pusey
Sep 10, 2016·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Lifeng HuangWenxiong Li
Feb 16, 2017·Current Opinion in Nephrology and Hypertension·Kerstin Ebefors, Jenny Nyström
Jun 16, 2017·Cell Death & Disease·Amy FearnNeil S Sheerin
Nov 9, 2017·International Journal of Molecular Medicine·Shuhei FukunagaTakuji Torimura
Feb 3, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Eva NüskenKai-Dietrich Nüsken
Mar 10, 2020·BioMed Research International·Ryosuke TakagiHiromichi Yumoto
Nov 23, 2019·International Journal of Molecular Sciences·Re-Wen WuFeng-Sheng Wang
Feb 6, 2021·Frontiers in Immunology·Grace R PidwillSimon J Foster
Jan 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Sladjana Skopelja-GardnerKeith B Elkon
Jan 21, 2019·Joint, Bone, Spine : Revue Du Rhumatisme·Xavier RomandAthan Baillet
Oct 26, 2021·The Kurume Medical Journal·Atsushi MoriTakuji Torimura

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