Cytokines have been regarded as effector molecules responsible for +-cell death and major histocompatibility complex hyperexpression in endocrine pancreas of type I diabetes. However, the mechanism that results in +-cell–selective destruction has not been elucidated. We demonstrated in this study, using cell lines of transformed mouse +-cells and α-cells, that only pancreatic +-cells but not α-cells produced tumor necrosis factor-α when exposed to interleukin-1 +. Northern blot analysis confirmed the +-cell-selective expression of tumor necrosis factor-α mRNA. Interleukin-1 + also provoked tumor necrosis factor-α mRNA expression in vitro by normal mouse islet cells. Because tumor necrosis factor-α has been shown to potentiate +-cell cytotoxicity of interleukin-1 and interferon-gamma, tumor necrosis factor-α produced in situ by +-cells might be self-destructive. In fact, a low dose of interleukin-1 + in combination with a low dose of interferon-gamma preferentially injured +-cells. Hence endogenous tumor necrosis factor-α production by +-cells may be involved in +-cell–selective destruction in type 1 diabetes.
Pancreatic β-Cell–Selective Production of Tumor Necrosis Factor-α Induced by Interleukin-1
Kentaro Yamada, Naoko Takane, Shuichi Otabe, Chizuko Inada, Masahiro Inoue, Kyohei Nonaka; Pancreatic β-Cell–Selective Production of Tumor Necrosis Factor-α Induced by Interleukin-1. Diabetes 1 July 1993; 42 (7): 1026–1031. https://doi.org/10.2337/diab.42.7.1026
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