IL-32γ overexpression accelerates streptozotocin (STZ)-induced type 1 diabetes

Interleukin-32 (IL-32) is a cytokine produced by T lymphocytes, natural killer (NK) cells, monocytes and epithelial cells. There are five splicing variants (alpha, beta, gamma, delta, and epsilon) and IL-32 gamma is the most active isoform. We generated human IL-32 gamma transgenic (IL-32 gamma TG) mice, displaying a high level of IL-32 gamma expression in the pancreas. We investigated the effect of IL-32 gamma on streptozotocin (STZ)-induced type I diabetes model using IL-32 gamma TG mice. After a suboptimal diabetogenic dose of STZ administration, IL-32 gamma TG mice showed significantly increased blood glucose level comparing with that of wild type (WT) mice at day 5. Inflammatory cytokines levels such as, IL-6, TNF alpha, IFN gamma and IL-1 beta, in pancreas and liver lysates were accessed by a specific cytokine ELISA. The proinflammatory cytokines were significantly enhanced in the pancreas of IL-32 gamma TG mice comparing to that of WT mice whereas those cytokines levels in liver of IL-32 gamma TG and WT mice were not changed by STZ. These data indicate that the overexpression of IL-32 gamma contributes to initial islet beta-cells injury and inflammation in pancreas and aggravates STZ-induced type 1 diabetes. (C) 2014 Elsevier Ltd. All rights reserved.