PERONE Marcelo Javier
Curcumin ameliorates autoimmune diabetes. Evidences in accelerated murine models of type 1 diabetes
CASTRO, CN; BARCALA TABARROZZI, AE; WINNEWISSER, J.; ANTUNICA NOGUEROL, M; LIBERMAN, AC; PAZ, D.A.; DEWEY, RA; PERONE, MJ
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
WILEY-BLACKWELL PUBLISHING, INC
Lugar: Londres; Año: 2014 p. 149 - 149
Type 1 diabetes (T1DM) is a T-cell mediated autoimmune disease that selectively destroys pancreatic cells. The only possible cure for T1DM is to control autoimmunity against cell specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T-cell response that destroys pancreatic cell to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: 1) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and 2) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset and in some instances prevented autoimmune diabetes by inhibiting pancreatic leukocyte infiltration and preserving insulin expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates T-lymphocyte response impairing proliferation and IFN production through modulation of T-bet, a key transcription factor for pro-inflammatory Th1 lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces NF-B activation in TCR-stimulated NOD lymphocytes. In addition, curcumin impairs the T-cell stimulatory function of dendritic cells with reduced secretion of pro-inflammatory cytokines and NO, low surface expression of coestimulatory molecules leading to an overall diminished antigen presenting cell activity. These in vitro effects correlated with ex vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for cell death.