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Type: Artigo de periódico
Title: Diacerhein downregulate proinflammatory cytokines expression and decrease the autoimmune diabetes frequency in nonobese diabetic (NOD) mice
Author: Malaguti, C
Vilella, CA
Vieira, KP
Souza, GHMF
Hyslop, S
Zollner, RD
Abstract: NOD mice are used as experimental models as they develop type 1 diabetes mellitus (DM-1) spontaneously, with a strong similarity to the human disease. Diabetes mellitus type 1 is characterized by the destruction of the islet, orchestrated by T lymphocytes that induce cytokine release like IL-1 beta, promoting an inflammatory process. Diacerhein has antiinflammatory properties, inhibiting IL-1. However, the mechanisms involved in immune modulation are not completely understood. In the present study, serum and pancreatic islets were isolated to investigate the relationship between IL-1 beta, IFN-gamma, IL-12 and TNF-alpha expression and diabetes onset, morphological aspects, and diacerhein dose dependence in animals treated with different doses (5, 10 and 50 mg/kg/day) and the control group (saline solution). The results demonstrated upregulation of mRNA islets and downregulation of the serum concentration of IL-1 0, IL-1 2 and TNF-a, in the group treated with 5 and 10 mg/kg/day diacerhein, when compared with the saline group, and increased IFN-gamma serum concentration in the group treated with 50 mg/kg/day. These results suggest that diacerhein in NOD mice, decreases, in a dose-dependent manner, the diabetes frequency downregulating proinflammatory cytokines, such as IL-1 beta, TNF-alpha, IFN-gamma and IL-12 at posttranscriptional or posttranslational level. Furthermore, using the HPLC method, diacerhein and rhein (active metabolite) were detected in serum and pancreas of treated mice. (C) 2008 Elsevier B.V. All rights reserved.
Subject: cytokines
autoimmune diabetes
Country: Holanda
Editor: Elsevier Science Bv
Rights: fechado
Identifier DOI: 10.1016/j.intimp.2008.01.020
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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