2026-04-17T12:26:00Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1200232025-12-05T13:19:00Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Ripoll Llagostera, Èlia author Ramon, Laura de author Bordignon Draibe, Juliana author Merino, Ana author Bolaños, Núria author Gomà, Montse author Cruzado, Josep Ma. author Grinyó Boira, Josep M. author Torras Ambròs, Joan author 2018-02-20T09:46:03Z 2018-02-20T09:46:03Z 2016-06-08 2018-02-20T09:46:03Z Es va publicar un erratum de l'article a: Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 152 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. Lupus Malalties autoimmunitàries Citoquines Ratolins (Animals de laboratori) Lupus Autoimmune diseases Cytokines Mice (Laboratory animals) JAK3-STAT pathway blocking benefits in experimental lupus nephritis