title: IL-27 inhibits hyperglycemia and pancreatic islet inflammation induced by streptozotocin in mice.
abstract: Inflammation driven by immune cells and pro-inflammatory cytokines is implicated in pancreatic β-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 α 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-1β 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-1β 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 β-cell protection in diabetes.
authors.affiliation: Department of Cardiovascular Medicine, Saga University Faculty of Medicine, Saga, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hirase
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hara
authors.forename: Noriko
authors.initials: N
authors.lastname: Ide-Iwata
authors.forename: Ai
authors.initials: A
authors.lastname: Nishimoto-Hazuku
authors.forename: Christiaan J M
authors.initials: CJ
authors.lastname: Saris
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001786:Blood Glucose / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020381:Interleukin-17 / Q000172:deficiency / Q000494:pharmacology*; D007515:Islets of Langerhans; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D010195:Pancreatitis / Q000517:prevention & control*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D013311:Streptozocin / Q000633:toxicity; D014162:Transfection
chemical_list: D000903:Antibiotics, Antineoplastic; D001786:Blood Glucose; D007004:Hypoglycemic Agents; C112441:IL27RA protein, human; C494200:Il6st protein, mouse; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130; D013311:Streptozocin