Administration of alpha-Galactosylceramide Improves Adenine-Induced Renal Injury

Autor(es):Mostrar menos -

Aguiar, Cristhiane Favero ^{[1, 2]} ; Naffah-de-Souza, Cristiane ^[2] ; Castoldi, Angela ^[2] ; Correa-Costa, Matheus ^[2] ; Braga, Tarcio T. ^[2] ; Naka, Erika L. ^[1] ; Amano, Mariane T. ^[2] ; Abate, Debora T. R. S. ^[2] ; Hiyane, Meire I. ^[2] ; Cenedeze, Marcos A. ^[1] ; Pacheco e Silva Filho, Alvaro ^{[1, 3]} ; Camara, Niels O. S. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, BR-05508900 Sao Paulo, SP - Brazil

^[3] Albert Einstein Hosp, Renal Transplantat Unit, Inst Israelita Ensino & Pesquisa Albert Einst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Medicine; v. 21, p. 553-562, 2015.
• Citações Web of Science: 5

Resumo

Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to alpha-galactosylceramide (alpha GalCer). alpha GalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-gamma and interleukin (IL)-4. NKT cells and IFN-gamma are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, J alpha 18KO and IFN-gamma KO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and J alpha 18KO mice exhibited renal dysfunction, but adenine-fed J alpha 18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-alpha and type I collagen. To analyze the role of activated iNKT cells in our model, we administered alpha GalCer in WT mice during adenine ingestion. After alpha GalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-gamma KO mice after alpha GalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-gamma production is one of the factors contributing to improved renal function after alpha GalCer administration. (AU)

• Processo FAPESP: 07/07139-3 - Investigando o papel da heme-oxigenase 1 em diferentes processos inflamatórios renais em modelos animais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/02270-2 - Novos mecanismos celulares, moleculares e imunológicos das lesões renais agudas e crônicas: busca por novas estratégias terapêuticas
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/16794-3 - Influência da microbiota intestinal na participação e no perfil das células NKT num modelo experimental de colite
• Beneficiário: Cristhiane Favero de Aguiar
• Modalidade de apoio: Bolsas no Brasil - Doutorado