T cells cooperate with palmitic acid in induction of beta cell apoptosis.
BACKGROUND
Diabetes is characterized by progressive failure of insulin producing beta cells. It is well known that both saturated fatty acids and various products of immune cells can contribute to the reduction of beta cell viability and functionality during diabetes pathogenesis. However, their joint action on beta cells has not been investigated, so far. Therefore, we explored the possibility that leukocytes and saturated fatty acids cooperate in beta cell destruction.


RESULTS
Rat pancreatic islets or insulinoma cells (RIN) were co-cultivated with concanavalin A (ConA)-stimulated rat lymph node cells (LNC), or they were treated with cell-free supernatants (Sn) obtained from ConA-stimulated spleen cells or from activated CD3+ cells, in the absence or presence of palmitic acid (PA). ConA-stimulated LNC or Sn and PA cooperated in inducing caspase-3-dependent RIN cell apoptosis. The observed effect of PA and Sn on RIN cell viability was mediated by p38 mitogen-activated protein kinase (MAPK)-signaling and was achieved through auto-destructive nitric oxide (NO) production. The cooperative effect of Sn was mimicked with the combination of interleukin-1beta, interleukin-2, interleukin-6, interleukin-17, interferon-gamma and tumor necrosis factor-alpha.


CONCLUSIONS
These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.
Cvjetićanin
Tamara
T
Department of Immunology, Institute for Biological Research Sinisa Stanković, University of Belgrade, Belgrade, Serbia. cvjetica@gmail.com
Stojanović
Ivana
I
Timotijević
Gordana
G
Stosić-Grujicić
Stanislava
S
Miljković
Djordje
D
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology; D007340:Insulinoma / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D019308:Palmitic Acid / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D019308:Palmitic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3