title: Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes.
abstract: OBJECTIVE
  We recently found that activation of the type III histone deacetylase sirtuin 1 suppresses T cell immune responses. Here we sought to determine the therapeutic potential of the sirtuin 1 activator resveratrol in the treatment of diabetes in the NOD mouse model of type 1 diabetes and the mechanisms underlying such potential.
  
  
  METHODS
  NOD mice were fed or subcutaneously injected with resveratrol and evaluated for development of diabetes. Splenocytes from resveratrol-treated and control mice were analysed by gene array. The altered expression of inflammatory genes induced by resveratrol was validated and the role of changed gene expression in prevention of diabetes was determined.
  
  
  RESULTS
  Resveratrol administration potently prevented and treated type 1 diabetes in NOD mice. Gene array analysis indicated a dramatic decrease in expression of Ccr6, which encodes chemokine (C-C motif) receptor (CCR) 6, in the splenocytes from resveratrol-treated mice. CCR6 abundance on IL-17-producing cells and CD11b(+)F4/80(hi) macrophages was inhibited by resveratrol treatment. Interestingly, CCR6(+) IL-17-producing cells and CD11b(+)F4/80(hi) macrophages accumulated in the spleens and pancreatic lymph nodes, but their presence in the pancreas was reduced, suggesting that resveratrol blocks their migration from peripheral lymphoid organs to the pancreas. Indeed, the migration of splenocytes toward media containing chemokine (C-C motif) ligand 20 (CCL20) was impaired by resveratrol treatment. CCL20 peptides, which block CCR6 binding to CCL20, inhibited development of type 1 diabetes.
  
  
  CONCLUSIONS
  Inhibition of CCR6-mediated migration of inflammatory cells by resveratrol may provide a powerful approach for treatment of type 1 diabetes and possibly of other inflammatory diseases.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL 60612, USA. leesangm@Northwestern.edu
authors.forename: S-M
authors.initials: SM
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: D M
authors.initials: DM
authors.lastname: Tartar
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: S Q
authors.initials: SQ
authors.lastname: Ye
authors.forename: H
authors.initials: H
authors.lastname: Zaghouani
authors.forename: D
authors.initials: D
authors.lastname: Fang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D054399:Receptors, CCR6 / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D007004:Hypoglycemic Agents; D020381:Interleukin-17; D054399:Receptors, CCR6; D013267:Stilbenes; D000077185:Resveratrol