dc.contributor |
Universitat de Barcelona |
dc.contributor.author |
Ripoll Llagostera, Èlia |
dc.contributor.author |
Ramon, Laura de |
dc.contributor.author |
Bordignon Draibe, Juliana |
dc.contributor.author |
Merino, Ana |
dc.contributor.author |
Bolaños, Núria |
dc.contributor.author |
Gomà, Montse |
dc.contributor.author |
Cruzado, Josep Ma. |
dc.contributor.author |
Grinyó Boira, Josep M. |
dc.contributor.author |
Torras Ambròs, Joan |
dc.date |
2018-02-20T09:46:03Z |
dc.date |
2018-02-20T09:46:03Z |
dc.date |
2016-06-08 |
dc.date |
2018-02-20T09:46:03Z |
dc.identifier.citation |
1478-6362 |
dc.identifier.citation |
666380 |
dc.identifier.uri |
http://hdl.handle.net/2445/120023 |
dc.format |
12 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
BioMed Central |
dc.relation |
Reproducció del document publicat a: https://doi.org/10.1186/s13075-016-1034-x |
dc.relation |
Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 134 |
dc.relation |
https://doi.org/10.1186/s13075-016-1034-x |
dc.rights |
cc-by (c) Ripoll Llagostera, Èlia et al., 2016 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.rights |
http://creativecommons.org/licenses/by/3.0/es |
dc.subject |
Lupus |
dc.subject |
Malalties autoimmunitàries |
dc.subject |
Citoquines |
dc.subject |
Ratolins (Animals de laboratori) |
dc.subject |
Lupus |
dc.subject |
Autoimmune diseases |
dc.subject |
Cytokines |
dc.subject |
Mice (Laboratory animals) |
dc.title |
JAK3-STAT pathway blocking benefits in experimental lupus nephritis |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |
dc.description.abstract |
Es va publicar un erratum de l'article a: Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 152 |
dc.description.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. |