Administration of alpha-Galactosylceramide Improves Adenine-Induced Renal Injury

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Molecular Medicine; v. 21, p. 553-562, 2015.
• Web of Science Citations: 5

Abstract

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)

• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/16794-3 - Influence of gut microbiota on NKT cells profile in an experimental model of colitis
• Grantee: Cristhiane Favero de Aguiar
• Support Opportunities: Scholarships in Brazil - Doctorate