IL-27 inhibits hyperglycemia and pancreatic islet inflammation induced by streptozotocin in mice

Hirokazu Fujimoto, Tetsuaki Hirase, Yoshiyuki Miyazaki, Hiromitsu Hara, Noriko Ide-Iwata, Ai Nishimoto-Hazuku, Christiaan J.M. Saris, Hiroki Yoshida, Koichi Node

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24 Citations (Scopus)

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 virusinduced 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.

Original languageEnglish
Pages (from-to)2327-2336
Number of pages10
JournalAmerican Journal of Pathology
Volume179
Issue number5
DOIs
Publication statusPublished - Nov 1 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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    Fujimoto, H., Hirase, T., Miyazaki, Y., Hara, H., Ide-Iwata, N., Nishimoto-Hazuku, A., Saris, C. J. M., Yoshida, H., & Node, K. (2011). IL-27 inhibits hyperglycemia and pancreatic islet inflammation induced by streptozotocin in mice. American Journal of Pathology, 179(5), 2327-2336. https://doi.org/10.1016/j.ajpath.2011.08.001