| First Author | Fujimoto H | Year | 2011 |
| Journal | Am J Pathol | Volume | 179 |
| Issue | 5 | Pages | 2327-36 |
| PubMed ID | 21925473 | Mgi Jnum | J:177366 |
| Mgi Id | MGI:5294862 | Doi | 10.1016/j.ajpath.2011.08.001 |
| Citation | Fujimoto H, et al. (2011) IL-27 Inhibits Hyperglycemia and Pancreatic Islet Inflammation Induced by Streptozotocin in Mice. Am J Pathol 179(5):2327-36 |
| abstractText | Inflammation driven by immune cells and pro-inflammatory cytokines is implicated in pancreatic beta-cell injury, leading to the development of diabetes mellitus. IL-27, a cytokine consisting of IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3), binds a membrane-bound heterodimeric receptor consisting of the IL-27 receptor alpha chain (WSX-1) and gp130. IL-27 has anti-inflammatory properties that regulate T-cell polarization and cytokine production. We evaluated blood glucose and islet proinsulin concentrations, inflammatory cell infiltration in islets, and expression of IL-1beta mRNA in pancreas in wild-type (WT), EBI3(-/-), and WSX-1(-/-) mice treated with streptozotocin (STZ). Hyperglycemia was augmented in EBI3(-/-) and WSX-1(-/-) mice compared with WT mice. Islet proinsulin levels after STZ treatment were lower in EBI3(-/-) and WSX-1(-/-) mice than in WT mice. The infiltration of islets by F4/80(+)CD11c(-)7/4(-) macrophages, CD4(+) T cells, and CD8(+) T cells was increased in EBI3(-/-) and WSX-1(-/-) mice compared with WT mice. The administration of recombinant IL-27, compared with control, decreased the blood glucose level, immune cell infiltration into islets, and IL-1beta mRNA expression in the pancreas and increased islet proinsulin levels in WT and EBI3(-/-) mice. Thus, IL-27 inhibits STZ-induced hyperglycemia and pancreatic islet inflammation in mice and represents a potential novel therapeutic approach for beta-cell protection in diabetes. |
