Involvement of c‐myc in the resistance of non‐obese diabetic mice to glucocorticoid‐induced apoptosis

• Published in: Immunology Vol. 95; no. 3; pp. 377 - 382
• Main Authors: Martins, T C, Aguas, A P
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-11-1998; Wiley Subscription Services, Inc
• Subjects: Animals; Apoptosis - genetics; Cells, Cultured; Dexamethasone - pharmacology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - pathology; Genes, myc; Lymphocytes - drug effects; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Proto-Oncogene Proteins c-myc - biosynthesis
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.1998.00600.x

Non‐obese diabetic (NOD) mice spontaneously develop insulin‐dependent diabetes mellitus (IDDM) as a consequence of autoimmune aggression of β cells of the endocrine pancreas by T cells. T lymphocytes of NOD mice are resistant to apoptosis induced by glucocorticoids, or by starving or DNA‐damaging treatments, a feature that was interpreted as being linked to escape of autoreactive T cells from thymic negative selection. c‐myc is one of the gene targets of glucocorticoids (GC), its expression being down‐regulated by the activated GC–GC receptor complex. We investigated here whether expression of Myc protein, in response to dexamethasone stimulation, was the same in NOD mice and in non‐autoimmune strains, namely NON, BALB/c and C57Bl.6. We found a consistent increase in the levels of Myc protein after GC‐treatment of lymphocytes of NOD mice, a finding that was in contrast to the down‐regulation of c‐myc that we observed in lymphocytes from mice not prone to diabetes. We also report that, rather than a absolute resistance to GC‐induced cell death, NOD mice display a delayed apoptotic response to GC. We propose that the resistance of NOD mice lymphocytes to GC‐induced apoptosis is because of inhibition of the repressive action of GC‐GR complexes at the level of c‐myc transcription. This deficient action of GC–GR results in increased production of nuclear Myc protein, peculiar to NOD mice cells, following their treatment with GC.