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Protective effect of nicotinamide and 3-aminobenzamide on islet cell damage induced by gamma-interferon and tumor
1Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Abstract:
Mouse islet cell monolayers were damaged when cultured for five days in a medium containing 200 U/ml of recombinant murine interferon-gamma (IFN-gamma) and 300 U/ml of recombinant tumor necrosis factor (TNF). The cells formed granular clusters and ultimately floated in the medium; the floating cells proved to be dead by the trypan-blue dye-exclusion method. When 20 mM of nicotinamide or 5 mM of 3-aminobenzamide was supplemented to the medium, islet cell monolayers remained in the presence of the cytokines. 51Cr release studies showed that specific 51Cr release during five-day incubation with 200 U/ml of IFN-gamma and 300 U/ml of TNF was 30 +/- 4% (mean +/- SE). In a medium containing 20 mM of nicotinamide, together with IFN-gamma and TNF, specific 51Cr release was significantly reduced (12 +/- 3%, p less than 0.01). 3-aminobenzamide was effective at the level of 5 mM; specific 51Cr release was 2 +/- 5% (p less than 0.01). These results suggest that the mechanism by which IFN-gamma and TNF damage islet cells may be similar to that of streptozotocin and/or alloxan.
Insights
Interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) damage mouse islet cells. Nicotinamide and 3-aminobenzamide protect these cells from cytokine-induced damage, suggesting a similar mechanism to alloxan.
Area of Science:
- Immunology
- Cell Biology
- Endocrinology
Background:
- Interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) are cytokines implicated in immune responses.
- Islet cells are crucial for insulin production and glucose regulation.
- Understanding the mechanisms of islet cell damage is vital for diabetes research.
Purpose of the Study:
- To investigate the cytotoxic effects of IFN-gamma and TNF on mouse islet cells.
- To determine if nicotinamide or 3-aminobenzamide can protect islet cells from cytokine-induced damage.
- To explore the potential mechanisms of IFN-gamma and TNF-mediated islet cell injury.
Main Methods:
- Mouse islet cell monolayers were cultured with recombinant murine IFN-gamma and TNF.
- Cell viability was assessed using the trypan-blue dye-exclusion method.
- Chromium-51 (51Cr) release assays were performed to quantify cell damage.
- Nicotinamide and 3-aminobenzamide were added to the culture medium to assess protective effects.
Main Results:
- Incubation with IFN-gamma and TNF for five days led to significant mouse islet cell damage and death.
- Supplementation with 20 mM nicotinamide or 5 mM 3-aminobenzamide protected islet cells from cytokine-induced toxicity.
- Specific 51Cr release was reduced from 30% to 12% with nicotinamide and 2% with 3-aminobenzamide (p < 0.01).
Conclusions:
- IFN-gamma and TNF induce significant damage to mouse islet cells in vitro.
- Nicotinamide and 3-aminobenzamide exhibit protective effects against IFN-gamma and TNF-induced islet cell injury.
- The mechanism of IFN-gamma and TNF-induced islet cell damage may resemble that of diabetogenic agents like streptozotocin and alloxan.