Effects of interleukin-15 on suppression of rat pancreatic islets in vitro induced by proinflammatory cytokines.
The cytokine IL-15 might contribute to inflammatory processes, but also act as an inhibitor of apoptosis in different cell lines. Furthermore, it has been reported that islet cells express IL-15 after exposure to proinflammatory cytokines, which could indicate a defence reaction. We aimed in this study to investigate if IL-15 could influence cell death and/or functional impairment of rat pancreatic islets induced by in vitro exposure to a combination of cytokines (25 U/ml IL-1beta+1000 U/ml IFN-gamma+1000 U/ml TNF-alpha). The effect of IL-15 itself on the function of rat pancreatic islets was also studied. Isolated rat islets were exposed for 24 h to IL-15 at different concentrations in the presence or absence of the cytokine mixture. The cytokines caused a strong inhibition of glucose-stimulated insulin release and the glucose oxidation rates. IL-15 (0.1-10 ng/ml) could not prevent the functional suppression caused by these effects. The cytokine combination caused a decline in whole islet DNA content and a marked increase in non-viable cells analysed by propidium iodide (PI) and annexin V staining. However, there was no significant decrease in whole islet DNA content when IL-15 (0.1 or 1.0 ng/ml) was present together with the cytokine mixture. On the other hand, IL-15 failed to influence the increase in cell death after PI and annexin V staining. If anything, IL-15 alone had a slight stimulatory effect (glucose oxidation rate) on islet cells. In conclusion, we can not exclude that IL-15 might antagonize some cytokine mediated cell death in islet cells, however, IL-15 fails to counteract functional suppression induced by cytokines.
Wallström
Johan
J
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Andersson
Annika K
AK
Sandler
Stellan
S
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000032:analysis / Q000235:genetics; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D007375:Interleukin-1; D019409:Interleukin-15; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA; D005947:Glucose