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Title: JAK3-STAT pathway blocking benefits in experimental lupus nephritis
Author: Ripoll Llagostera, Èlia
Ramon, Laura de
Bordignon Draibe, Juliana
Merino, Ana
Bolaños, Núria
Gomà, Montse
Cruzado, Josep Ma.
Grinyó Boira, Josep M.
Torras Ambròs, Joan
Keywords: Lupus
Malalties autoimmunitàries
Ratolins (Animals de laboratori)
Autoimmune diseases
Mice (Laboratory animals)
Issue Date: 8-Jun-2016
Publisher: BioMed Central
Abstract: Background: Lupus nephritis (LN) is a complex chronic autoimmune disease of unknown etiology characterized by loss of tolerance against several self-antigens. Cytokines are known to be central players in LN pathogenesis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is one important pathway that mediates signal transduction of several cytokines. In this study, we examined the pathogenic role of this pathway and how CP-690,550 treatment influences LN outcome. Methods: Six-month-old NZB/NZWF1 mice were divided into two different treatment groups: (1) control animals given vehicle treatment, cyclophosphamide, and mycophenolate mofetil treatment as positive controls of the therapy and (2) mice treated with CP-690,550, a JAK3 inhibitor. Mice were treated for 12 weeks. We evaluated renal function, anti-double-stranded DNA (anti-dsDNA) antibody, renal histology changes, kidney complement and immunoglobulin G (IgG) deposits, T-cell and macrophage infiltration, kidney inflammatory gene expression, and circulating cytokine changes. Results: CP-690,550 treatment significantly reduced proteinuria and improved renal function and histological lesions of the kidney. Compared with vehicle-treated animals, those undergoing CP-690,550 treatment showed significantly diminished anti-dsDNA antibody and complement component C3 and IgG deposition in glomeruli. We also observed a significant reduction of T-cell and macrophage infiltration. Kidney gene expression revealed a reduction in inflammatory cytokines and complement and related macrophage-attracting genes. Circulating inflammatory cytokines were also reduced with treatment. Conclusions: On the basis of our results, we conclude that the JAK-STAT pathway is implicated in the progression of renal inflammation in NZB/WF1 mice and that targeting JAK3 with CP-690,550 is effective in slowing down the course of experimental LN. Thus, CP-690,550 could become a new therapeutic tool in LN and other autoimmune diseases.
Note: Es va publicar un erratum de l'article a: Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 152
Note: Reproducció del document publicat a:
It is part of: Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 134
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ISSN: 1478-6362
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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