Research article

T cells cooperate with palmitic acid in induction of beta cell apoptosis

Tamara Cvjetićanin¹ , Ivana Stojanović¹ , Gordana Timotijević² , Stanislava Stošić-Grujičić¹ and Djordje Miljković¹

¹Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia

²Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia

author email corresponding author email

BMC Immunology 2009, 10:29doi:10.1186/1471-2172-10-29

Published:	22 May 2009

Abstract

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-1β, interleukin-2, interleukin-6, interleukin-17, interferon-γ and tumor necrosis factor-α.

Conclusion

These results imply that stimulated T cells produce cytokines that cooperate with saturated free fatty acids in beta cell destruction during diabetes pathogenesis.