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Interleukin 17A promotes diabetic kidney injury.
Ma, Jin; Li, Yan J; Chen, Xiaochen; Kwan, Tony; Chadban, Steven J; Wu, Huiling.
Afiliação
  • Ma J; Kidney Node Laboratory, The Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
  • Li YJ; Kidney Node Laboratory, The Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
  • Chen X; Kidney Node Laboratory, The Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
  • Kwan T; Kidney Node Laboratory, The Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
  • Chadban SJ; Kidney Node Laboratory, The Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, Australia.
  • Wu H; Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia.
Sci Rep ; 9(1): 2264, 2019 02 19.
Article em En | MEDLINE | ID: mdl-30783187
ABSTRACT
The role of the pro-inflammatory cytokine IL-17 in the pathogenesis of numerous inflammatory disorders is well-documented, but conflicting results are reported for its role in diabetic nephropathy. Here we examined the role of IL-17 signalling in a model of streptozotocin-induced diabetic nephropathy through IL-17 knockout mice, administration of neutralising monoclonal anti-IL-17 antibody and in vitro examination of gene expression of renal tubular cells and podocytes under high glucose conditions with or without recombinant IL-17. IL-17 deficient mice were protected against progression of diabetic nephropathy, exhibiting reduced albuminuria, glomerular damage, macrophage accumulation and renal fibrosis at 12 weeks and 24 weeks. Administration of anti-IL-17 monoclonal antibody to diabetic wild-type mice was similarly protective. IL-17 deficiency also attenuated up-regulation of pro-inflammatory and pro-fibrotic genes including IL-6, TNF-α, CCL2, CXCL10 and TGF-ß in diabetic kidneys. In vitro co-stimulation with recombinant IL-17 and high glucose were synergistic in increasing the expression of pro-inflammatory genes in both cultured renal tubular cells and podocytes. We conclude that absence of IL-17 signalling is protective against streptozotocin-induced diabetic nephropathy, thus implying a pro-inflammatory role of IL-17 in its pathogenesis. Targeting the IL-17 axis may represent a novel therapeutic approach in the treatment of this disorder.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-17 / Diabetes Mellitus Experimental / Nefropatias Diabéticas / Rim Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-17 / Diabetes Mellitus Experimental / Nefropatias Diabéticas / Rim Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article