IL-27 Inhibits Hyperglycemia and Pancreatic Islet Inflammation Induced by Streptozotocin in Mice
| Autor: | Yoshiyuki Miyazaki, Hirokazu Fujimoto, Hiroki Yoshida, Hiromitsu Hara, Koichi Node, Ai Nishimoto-Hazuku, Christiaan J. M. Saris, Noriko Ide-Iwata, Tetsuaki Hirase |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
endocrine system medicine.medical_specialty endocrine system diseases Neutrophils medicine.medical_treatment Gene Expression Inflammation Biology Transfection Streptozocin Pathology and Forensic Medicine Islets of Langerhans Mice Internal medicine Cytokine Receptor gp130 medicine Animals Hypoglycemic Agents Proinsulin geography Antibiotics Antineoplastic geography.geographical_feature_category Interleukin-17 Regular Article EBI3 Receptors Interleukin Islet Streptozotocin Recombinant Proteins Mice Inbred C57BL medicine.anatomical_structure Cytokine Endocrinology Pancreatitis Hyperglycemia Interleukin 17 medicine.symptom Pancreas Immunosuppressive Agents Signal Transduction medicine.drug |
| Zdroj: | The American Journal of Pathology. 179:2327-2336 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2011.08.001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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