Apoptosis of Human Islet Cells by Cytokines

Overview

Journal Immune Netw

Specialty Allergy & Immunology

Date 2012 Aug 24

PMID 22916047

Citations 8

Authors

Sunshin Kim

Kyoung-Ah Kim

Kyoungho Suk

Yun-Hee Kim

Seung Hoon Oh

Moon-Kyu Lee

Kwang-Won Kim

Myung-Shik Lee

Affiliations

Soon will be listed here.

Abstract

FasL, perforin, TNFα, IL-1 and NO have been considered as effector molecule(s) leading to β-cell death in autoimmune diabetes. However, the real culprit(s) of β-cell destruction have long been elusive despite intense investigation. Previously we have suggested IFNγ/TNFα synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of IFNγ and TNFα but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. IFNγ treatment conferred susceptibility to TNFα-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that IFNγ/TNFα synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by IFNγ treatment in human islet cells. Taken together, we suggest that IFNγ/TNFα synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

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References

Barthson J, Germano C, Moore F, Maida A, Drucker D, Marchetti P . Cytokines tumor necrosis factor-α and interferon-γ induce pancreatic β-cell apoptosis through STAT1-mediated Bim protein activation. J Biol Chem. 2011; 286(45):39632-43. PMC: 3234786. DOI: 10.1074/jbc.M111.253591. View

Turley S, Poirot L, Hattori M, Benoist C, Mathis D . Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med. 2003; 198(10):1527-37. PMC: 2194112. DOI: 10.1084/jem.20030966. View

Amrani A, Verdaguer J, Anderson B, Utsugi T, Bou S, Santamaria P . Perforin-independent beta-cell destruction by diabetogenic CD8(+) T lymphocytes in transgenic nonobese diabetic mice. J Clin Invest. 1999; 103(8):1201-9. PMC: 408282. DOI: 10.1172/JCI6266. View

Rabinovitch A, Sumoski W, Rajotte R, Warnock G . Cytotoxic effects of cytokines on human pancreatic islet cells in monolayer culture. J Clin Endocrinol Metab. 1990; 71(1):152-6. DOI: 10.1210/jcem-71-1-152. View

Wang Y, Pontesilli O, Gill R, La Rosa F, Lafferty K . The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice. Proc Natl Acad Sci U S A. 1991; 88(2):527-31. PMC: 50844. DOI: 10.1073/pnas.88.2.527. View

Suk K, Kim S, Kim Y, Kim K, Chang I, Yagita H . IFN-gamma/TNF-alpha synergism as the final effector in autoimmune diabetes: a key role for STAT1/IFN regulatory factor-1 pathway in pancreatic beta cell death. J Immunol. 2001; 166(7):4481-9. DOI: 10.4049/jimmunol.166.7.4481. View

Kim S, Kim H, Chung K, Oh S, Yun J, Im S . Essential role for signal transducer and activator of transcription-1 in pancreatic beta-cell death and autoimmune type 1 diabetes of nonobese diabetic mice. Diabetes. 2007; 56(10):2561-8. DOI: 10.2337/db06-1372. View

Suk K, Chang I, Kim Y, Kim S, Kim J, Kim H . Interferon gamma (IFNgamma ) and tumor necrosis factor alpha synergism in ME-180 cervical cancer cell apoptosis and necrosis. IFNgamma inhibits cytoprotective NF-kappa B through STAT1/IRF-1 pathways. J Biol Chem. 2001; 276(16):13153-9. DOI: 10.1074/jbc.M007646200. View

Rabinovitch A, Suarez-Pinzon W, Strynadka K, Schulz R, Lakey J, Warnock G . Human pancreatic islet beta-cell destruction by cytokines is independent of nitric oxide production. J Clin Endocrinol Metab. 1994; 79(4):1058-62. DOI: 10.1210/jcem.79.4.7962274. View

10.

Katz J, Benoist C, Mathis D . T helper cell subsets in insulin-dependent diabetes. Science. 1995; 268(5214):1185-8. DOI: 10.1126/science.7761837. View

11.

Wicker L, Miller B, Mullen Y . Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice. Diabetes. 1986; 35(8):855-60. DOI: 10.2337/diab.35.8.855. View

12.

Kim H, Han M, Chung K, Kim S, Kim E, Kim M . Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes. Immunity. 2007; 27(2):321-33. DOI: 10.1016/j.immuni.2007.06.010. View

13.

Kurrer M, Pakala S, HANSON H, Katz J . Beta cell apoptosis in T cell-mediated autoimmune diabetes. Proc Natl Acad Sci U S A. 1997; 94(1):213-8. PMC: 19288. DOI: 10.1073/pnas.94.1.213. View

14.

Kim S, Kim K, Hwang D, Lee T, Kayagaki N, Yagita H . Inhibition of autoimmune diabetes by Fas ligand: the paradox is solved. J Immunol. 2000; 164(6):2931-6. DOI: 10.4049/jimmunol.164.6.2931. View

15.

Marselli L, Dotta F, Piro S, Santangelo C, Masini M, Lupi R . Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines. J Clin Endocrinol Metab. 2001; 86(10):4974-8. DOI: 10.1210/jcem.86.10.7938. View

16.

Delaney C, Pavlovic D, Hoorens A, Pipeleers D, Eizirik D . Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells. Endocrinology. 1997; 138(6):2610-4. DOI: 10.1210/endo.138.6.5204. View

17.

Ricordi C, Lacy P, FINKE E, Olack B, Scharp D . Automated method for isolation of human pancreatic islets. Diabetes. 1988; 37(4):413-20. DOI: 10.2337/diab.37.4.413. View

18.

Kim Y, Kim S, Kim K, Yagita H, Kayagaki N, Kim K . Apoptosis of pancreatic beta-cells detected in accelerated diabetes of NOD mice: no role of Fas-Fas ligand interaction in autoimmune diabetes. Eur J Immunol. 1999; 29(2):455-65. DOI: 10.1002/(SICI)1521-4141(199902)29:02<455::AID-IMMU455>3.0.CO;2-A. View