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Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2
H Iwahashi1, T Hanafusa, Y Eguchi
1Second Department of Internal Medicine, Osaka University Medical School, Japan.
Abstract:
Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-1 beta, tumour necrosis factor-alpha, and interferon-gamma) induced apoptotic cell death in the mouse pancreatic beta-cell line beta TC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line alpha TC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than in beta TC1 cells. The abundance of endogenous Bcl-2 in beta TC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in beta TC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells.
Insights
Cytokines induce apoptosis, a form of cell death, in pancreatic beta cells, contributing to type 1 diabetes. Bcl-2 protein helps protect these vital insulin-producing cells.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Pancreatic beta-cell destruction is implicated in insulin-dependent diabetes mellitus.
- Understanding the molecular mechanisms of beta-cell death is crucial for disease intervention.
Purpose of the Study:
- To investigate the molecular mechanisms of cytokine-induced beta-cell death.
- To determine the role of Bcl-2 in protecting pancreatic islet cells from apoptosis.
Main Methods:
- Utilized mouse pancreatic beta-cell lines (beta TC1, NIT-1) and alpha-cell line (alpha TC1).
- Exposed cell lines to a combination of three cytokines: interleukin-1 beta, tumour necrosis factor-alpha, and interferon-gamma.
- Assessed apoptosis through hypodiploid nuclei and DNA fragmentation.
- Manipulated Bcl-2 expression levels in beta TC1 cells.
Main Results:
- A combination of three cytokines induced apoptotic cell death in beta TC1 cells, evidenced by hypodiploid nuclei and DNA fragmentation.
- Apoptosis was also induced in alpha TC1 and NIT-1 cells, but to a lesser extent.
- Beta TC1 cells exhibited lower endogenous Bcl-2 abundance compared to other cell lines.
- Overexpression of human Bcl-2 partially protected beta TC1 cells from cytokine-induced apoptosis.
Conclusions:
- Cytokine-induced apoptosis plays a significant role in pancreatic beta-cell destruction.
- Bcl-2 acts as a protective factor against apoptosis in pancreatic islet cells.