Tunicamycin Inhibits Diabetes

Background: Autoimmune diseases are characterized by a breakdown of immunologic tolerance, and this breakdown can lead to life-threatening or lifelong disorders. Moreover; drugs that are used to treat these diseases are few in number and are associated with many serious adverse effects. Methods: We used the rat insulin promoter-glycoprotein mouse model to analyze the role of tunicamycin in the process of autoimmune diabetes; the P14 mouse model to analyze the effect of tunicamycin on CD8+ T cells; chop knockout mice to analyze the role of tunicamycin on an endoplasmic reticulum stress model; and fluorescence-activated cell sorting, quantitative real-time polymerase chain reaction, and histologic methods. Results: We found that a single dose of tunicamycin reduced the activation and pancreatic infiltration of CD8+ T cells. This activity delayed the incidence of virus-induced diabetes and improved survival rates. Conclusion: Tunicamycin may offer therapeutic opportunities for T cell-mediated autoimmune diseases such as diabetes.

[1]  W. Brück,et al.  Oxidized ATP inhibits T‐cell‐mediated autoimmunity , 2010, European journal of immunology.

[2]  Nathan L. Vanderford.  Defining the regulation of IL-1β- and CHOP-mediated β-cell apoptosis , 2010, Islets.

[3]  E. Schwiebert.  Underlying purinergic signaling contributes to T lymphocyte activation in tissue repair. Focus on "shockwaves increase the T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation". , 2010, American journal of physiology. Cell physiology.

[4]  L. V. Van Gaal,et al.  Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. , 2009, The Netherlands journal of medicine.

[5]  Subramaniam Pennathur,et al.  Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes. , 2008, The Journal of clinical investigation.

[6]  Xianglin Shi,et al.  Brain‐derived neurotrophic factor suppresses tunicamycin‐induced upregulation of CHOP in neurons , 2007, Journal of neuroscience research.

[7]  S. Akira,et al.  Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling. , 2006, The Journal of clinical investigation.

[8]  R. Zinkernagel,et al.  Do thymically and strictly extrathymically developing T cells generate similar immune responses? , 2004, Blood.

[9]  S. Oyadomari,et al.  hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria , 2004, Cell Death and Differentiation.

[10]  R. Zinkernagel,et al.  Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  N. Rose,et al.  Type 1 diabetes: virus infection or autoimmune disease? , 2002, Nature Immunology.

[12]  P. Pozzilli,et al.  Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention. , 2001, Diabetes care.

[13]  Michael J. Parsons,et al.  Negative Regulation of T Cell Proliferation and Interleukin 2 Production by the Serine Threonine Kinase Gsk-3 , 2000, The Journal of experimental medicine.

[14]  R. Zinkernagel,et al.  FTY720 Immunosuppression Impairs Effector T Cell Peripheral Homing Without Affecting Induction, Expansion, and Memory1 , 2000, The Journal of Immunology.

[15]  T. Ohtsubo,et al.  Inhibition of N‐linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head‐and‐neck carcinoma cells , 1999, International journal of cancer.

[16]  A. Tordai,et al.  Tunicamycin inhibits the expression of functional thrombin receptors on human T-lymphoblastoid cells. , 1995, Biochemical and biophysical research communications.

[17]  H. Pircher,et al.  Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice , 1991, Cell.

[18]  H. Pircher,et al.  Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen , 1989, Nature.

[19]  D. Bar-Sagi,et al.  Effect of tunicamycin, an inhibitor of protein glycosylation, on the biological properties of acetylcholine receptor in cultured muscle cells. , 1983, The Journal of biological chemistry.

[20]  F. Bach,et al.  The role of gp70 in the target antigen recognized by murine leukemia virus immune cytotoxic T‐lymphocytes , 1980, International journal of cancer.

[21]  K. Olden,et al.  Selective cytotoxicity of tunicamycin for transformed cells , 1979, International journal of cancer.

[22]  D. Banerjee,et al.  Tunicamycin inhibits capillary endothelial cell proliferation by inducing apoptosis. Targeting dolichol-pathway for generation of new anti-angiogenic therapeutics. , 2000, Advances in experimental medicine and biology.