Ingested (oral) SIRS peptide 1-21 suppresses type 1 diabetes in NOD mice.
Type 1 diabetes (T1D) is a chronic disorder that results from autoimmune destruction of the insulin-producing pancreatic beta cell. The nonobese diabetic (NOD) mouse is a model of the human autoimmune disease T1D. Soluble immune response suppressor (SIRS) is a nonspecific protein suppressor of immune response produced by immunomodulatory T cells stimulated by type I interferon (IFN). SIRS inhibits antibody responses in vivo, lipopolysaccharide (LPS)-induced fever, and delayed-type hypersensitivity (DTH) responses. Previous investigators have isolated the N-terminal sequence of SIRS protein consisting of 21 amino acids. Mice ingesting 1 microg SIRS peptide 1-21 showed significant delayed onset of T1D and a decreased frequency of T1D compared with mock-fed and 10-microg-fed mice and a significant decrease in islet inflammation. There were significant decreases in islet lymphocyte chemokine production of granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein-1 gamma (MIP-1 gamma), regulated upon activation, normal T cell-expressed, and presumably secreted (RANTES), and stromal cell-derived factor-1 (SDF-1) in the SIRS-fed mice, factors important in migration of inflammatory cell into the islets. Ingested (oral) SIRS peptide inhibits clinical T1D by decreasing target organ cellular migration of islet destructive populations by suppression of islet lymphocyte chemokine secretion.
Brod
Staley A
SA
Multiple Sclerosis Research Group, Department of Neurology, University of Texas-Houston, Houston, TX 77030, USA. staley.a.brod@uth.tmc.edu
Hood
Zachary
Z
D000284:Administration, Oral; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D007249:Inflammation; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D013491:Suppressor Factors, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology*
D018925:Chemokines; D010446:Peptide Fragments; D013491:Suppressor Factors, Immunologic; C013256:soluble immune response suppressor