Cytokine signalling in the β-cell: A dual role for IFNγ

Biochemical Society Transactions

Volumn 36, Issue 3, 2008, Pages 328-333

  Gysemans, Conny ^a   Callewaert, Hanne ^a   Overbergh, Lutgart ^a   Mathieu, Chantal ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

cell; Cytokine; Diabetes; Interferon (IFN ); Janus kinase (JAK); Signal transducer and activator of transcription (STAT)

Indexed keywords

CYTOKINE; GAMMA INTERFERON; INTERFERON REGULATORY FACTOR 1; INTERLEUKIN 1BETA; JANUS KINASE; STAT1 PROTEIN; SUMO PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING;

APOPTOSIS; CELL ACTIVITY; CELL DEATH; CELL FUNCTION; CONFERENCE PAPER; CYTOKINE PRODUCTION; IMMUNE SYSTEM; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PANCREAS ISLET; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEOMICS; STREPTOZOCIN DIABETES;

ANIMALS; HUMANS; INSULIN-SECRETING CELLS; INTERFERON REGULATORY FACTOR-1; INTERFERON TYPE II; JANUS KINASES; SIGNAL TRANSDUCTION; STAT1 TRANSCRIPTION FACTOR;

MUS;

EID: 45249106869     PISSN: 03005127     EISSN: None     Source Type: Journal    
DOI: 10.1042/BST0360328     Document Type: Conference Paper

References (55)

1. Sutton, V.R., Estella, E., Li, C., Chen, M., Thomas, H.E., Kay, T.W. and Trapani, J.A. (2006) A critical role for granzyme B, in addition to perforin and TNF-α, in alloreactive CTL-induced mouse pancreatic β-cell death. Transplantation 81, 146-154
2. Dudek, N.L., Thomas, H.E., Mariana, L., Sutherland, R.M., Allison, J., Estella, E., Angstetra, E., Trapani, J.A., Santamaria, P., Lew, A.M. and Kay, T.W. (2006) Cytotoxic T-cells from T-cell receptor transgenic NOD8.3 mice destroy β-cells via the perforin and Fas pathways. Diabetes 55, 2412-2418
3. McKenzie, M.D., Dudek, N.L., Mariana, L., Chong, M.M., Trapani, J.A., Kay, T.W. and Thomas, H.E. (2006) Perforin and Fas induced by IFN-γ and TNF-α mediate β-cell death by OT-I CTL. Int. Immunol. 18, 837-846
4. Eizirik, D.L., Sandler, S., Welsh, N., Cetkovic-Cvrlje, M., Nieman, A., Geller, D.A., Pipeleers, D.G., Bendtzen, K. and Hellerstrom, C. (1994) Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J. Clin. Invest. 93, 1968-1974
5. Suk, K., Kim, S., Kim, Y.H., Kim, K.A., Chang, I., Yagita, H., Shong, M. and Lee, M.S. (2001) IFN-γ/TNF-α synergism as the final effector in autoimmune diabetes: a key role for STAT-1/IFN regulatory factor-1 pathway in pancreatic β-cell death. J. Immunol. 166, 4481-4489
6. Liu, D., Cardozo, A.K., Darville, M.I. and Eizirik, D.L. (2002) dsRNA cooperates with interferon-γ and IL-1β to induce both chemokine expression and nuclear factor-κB-dependent apoptosis in pancreatic β-cells: potential mechanisms for viral-induced insulitis and β-cell death in type 1 diabetes mellitus. Endocrinology 143, 1225-1234
7. Thomas, H.E., Darwiche, R., Corbett, J.A. and Kay, T.W. (2002) lnterleukin-1 plus γ-interferon-induced pancreatic β-cell dysfunction is mediated by β-cell nitric oxide production. Diabetes 51, 311-316
8. Cardozo, A.K., Kruhoffer, M., Leeman, R., Orntoft, T. and Eizirik, D.L. (2001) Identification of novel cytokine-induced genes in pancreatic β-cells by high-density oligonucleotide arrays. Diabetes 50, 909-920
9. Kutlu, B., Cardozo, A.K., Darville, M.I., Kruhoffer, M., Magnusson, N., Orntoft, T. and Eizirik, D.L. (2003) Discovery of gene networks regulating cytokine-induced dysfunction and apoptosis in insulin-producing INS-1 cells. Diabetes 52, 2701-2719
10. Rasschaert, J., Liu, D., Kutlu, B., Cardozo, A.K., Kruhoffer, M., Orntoft, T.F. and Eizirik, D.L. (2003) Global profiling of dsRNA- and IFN-γ-induced genes in rat pancreatic β-cells. Diabetologia 46, 1641-1657
11. D'Hertog, W., Overbergh, L., Lage, K., Ferreira, G.B., Maris, M., Gysemans, C., Flamez, D., Cardozo, A.K., Van den Bergh, B., Schoofs, L. et al. (2007) Proteomic analysis of cytokine-induced dysfunction and death in insulin producing INS-1E cells: new insights into the pathways involved. Mol. Cell. Proteomics. 6, 2180-2199
12. 2+, leading to induction of endoplasmic reticulum stress in pancreatic β-cells. Diabetes 54, 452-461
13. Cardozo, A.K., Heimberg, H., Heremans, Y., Leeman, R., Kutlu, B., Kruhoffer, M., Orntoft, T. and Eizirik, D.L. (2001) A comprehensive analysis of cytokine-induced and nuclear factor-κB-dependent genes in primary rat pancreatic β-cells. J. Biol. Chem. 276, 48879-48886
14. Ortis, F., Cardozo, A.K., Crispim, D., Storling, J., Mandrup-Poulsen, T. and Eizirik, D.L. (2006) Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-κB activation. Mol. Endocrinol. 20, 1867-1879
15. Rasschaert, J., Ladriere, L., Urbain, M., Dogusan, Z., Katabua, B., Sato, S., Akira, S., Gysemans, C., Mathieu, C. and Eizirik, D.L. (2005) Toll-like receptor 3 and STAT-1 contribute to dsRNA + interferon-γ-induced apoptosis in primary pancreatic β-cells. J. Biol. Chem. 280, 33984-33991
16. Briscoe, J., Kohlhuber, F. and Muller, M. (1996) JAKs and STATs branch out. Trends Cell Biol. 6, 336-340
17. Levy, D.E. and Darnell, Jr, J.E. (2002) STATs: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3, 651-662
18. 727 phosphorylation, differentially affecting specific target gene expression. EMBO J. 20, 91-100
19. Ungureanu, D., Vanhatupa, S., Kotaja, N., Yang, J., Aittomaki, S., Janne, O.A., Palvimo, J.J. and Silvennoinen, O. (2003) PIAS proteins promote SUMO-1 conjugation to STAT-1. Blood 102, 3311-3313
20. Durbin, J.E., Hackenmiller, R., Simon, M.C. and Levy, D.E. (1996) Targeted disruption of the mouse STAT-1 gene results in compromised innate immunity to viral disease. Cell 84, 443-450
21. Ramana, C.V., Kumar, A. and Enelow, R. (2005) STAT-1-independent induction of SOCS-3 by interferon-γ is mediated by sustained activation of STAT-3 in mouse embryonic fibroblasts. Biochem. Biophys. Res. Commun. 327, 727-733
22. Alexander, W.S., Starr, R., Metcalf, D., Nicholson, S.E., Farley, A., Elefanty, A.G., Brysha, M., Kile, B.T., Richardson, R., Baca, M. et al. (1999) Suppressors of cytokine signalling (SOCS): negative regulators of signal transduction. J. Leukocyte Biol. 66, 588-592
23. Liu, B., Liao, J., Rao, X., Kushner, S.A., Chung, C.D., Chang, D.D. and Shuai, K. (1998) Inhibition of STAT-1-mediated gene activation by PIAS-1. Proc. Natl. Acad. Sci. U.S.A. 95, 10626-10631
24. Sarvetnick, N., Liggitt, D., Pitts, S.L., Hansen, S.E. and Stewart, T.A. (1988) Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-γ. Cell 52, 773-782
25. Kay, T.W., Campbell, I.L., Oxbrow, L. and Harrison, L.C. (1991) Overexpression of class I major histocompatibility complex accompanies insulitis in the non-obese diabetic mouse and is prevented by anti-interferon-γ antibody. Diabetologia 34, 779-785
26. Debray-Sachs, M., Carnaud, C., Boitard, C., Cohen, H., Gresser, I., Bedossa, P. and Bach, J.F. (1991) Prevention of diabetes in NOD mice treated with antibody to murine IFN-γ. J. Autoimmun. 4, 237-248
27. von Herrath, M.G. and Oldstone, M.B. (1997) Interferon-γ is essential for destruction of β-cells and development of insulin-dependent diabetes mellitus. J. Exp. Med. 185, 531-539
28. Hultgren, B., Huang, X., Dybdal, N. and Stewart, T.A. (1996) Genetic absence of γ-interferon delays but does not prevent diabetes in NOD mice. Diabetes 45, 812-817
29. Gysemans, C.A., Pavlovic, D., Bouillon, R., Eizirik, D.L. and Mathieu, C. (2001) Dual role of interferon-γ signalling pathway in sensitivity of pancreatic β-cells to immune destruction. Diabetologia 44, 567-574
30. Serreze, D.V., Post, C.M., Chapman, H.D., Johnson, E.A., Lu, B. and Rothman, P.B. (2000) Interferon-γ receptor signalling is dispensable in the development of autoimmune type 1 diabetes in NOD mice. Diabetes 49, 2007-2011
31. Thomas, H.E., Parker, J.L., Schreiber, R.D. and Kay, T.W. (1998) IFN-γ action on pancreatic β-cells causes class I MHC upregulation but not diabetes. J. Clin. Invest. 102, 1249-1257
32. Wang, B., André, I., Gonzalez, A., Katz, J.D., Aguet, M., Benoist, C. and Mathis, D. (1997) Interferon-γ impacts at multiple points during the progression of autoimmune diabetes. Proc. Natl. Acad. Sci. U.S.A. 94, 13844-13849
33. Kanagawa, O., Xu, G., Tevaarwerk, A. and Vaupel, B.A. (2000) Protection of non-obese diabetic mice from diabetes by gene(s) closely linked to IFN-γ receptor loci. J. Immunol. 164, 3919-3923
34. Eizirik, D.L., Flodstrom, M., Karlsen, A.E. and Welsh, N. (1996) The harmony of the spheres: inducible nitric oxide synthase and related genes in pancreatic β-cells. Diabetologia 39, 875-890
35. Chen, G., Hohmeier, H.E. and Newgard, C.B. (2001) Expression of the transcription factor STAT-1α in insulinoma cells protects against cytotoxic effects of multiple cytokines. J. Biol. Chem. 276, 766-772
36. Gysemans, C.A., Ladriere, L., Callewaert, H., Rasschaert, J., Flamez, D., Levy, D.E., Matthys, P., Eizirik, D.L. and Mathieu, C. (2005) Disruption of the γ-interferon signalling pathway at the level of signal transducer and activator of transcription-1 prevents immune destruction of β-cells. Diabetes 54, 2396-2403
37. Leiter, E.H. (2002) Mice with targeted gene disruptions or gene insertions for diabetes research: problems, pitfalls, and potential solutions. Diabetologia 45, 296-308
38. Kim, S., Kim, H.S., Chung, K.W., Oh, S.H., Yun, J.W., Im, S.H., Lee, M.K., Kim, K.W. and Lee, M.S. (2007) Essential role for signal transducer and activator of transcription-1 in pancreatic β-cell death and autoimmune type 1 diabetes of nonobese diabetic mice. Diabetes 56, 2561-2568
39. Callewaert, H.I., Gysemans, C.A., Ladrière, L., D'Hertog, W., Hagenbrock, J., Overbergh, L., Eizirik, D.L. and Mathieu, C. (2007) Deletion of STAT-1 pancreatic islets protects against streptozotocin-induced diabetes and early graft failure but not against late rejection. Diabetes 56, 2169-2173
40. Cottet, S., Dupraz, P., Hamburger, F., Dolci, W., Jaguet, M. and Thorens, B. (2001) SOCS-1 protein prevents Janus kinase/STAT-dependent inhibition of β-cell insulin gene transcription and secretion in response to interferon-γ. J. Biol. Chem. 276, 25862-25870
41. Chong, M.M., Thomas, H.E. and Kay, T.W. (2002) Suppressor of cytokine signalling-1 regulates the sensitivity of pancreatic β-cells to tumour necrosis factor. J. Biol. Chem. 277, 27945-27952
42. Flodstrom-Tullberg, M., Yadav, D., Hagerkvist, R., Tsai, D., Secrest, P., Stotland, A. and Sarvetnick, N. (2003) Target cell expression of suppressor of cytokine signalling-1 prevents diabetes in the NOD mouse. Diabetes 52, 2696-2700
43. + T cell-mediated autoimmune destruction. J. Immunol. 172, 5714-5721
44. Solomon, M., Flodstrom-Tullberg, M. and Sarvetnick, N. (2005) Differences in suppressor of cytokine signalling-1 (SOCS-1) expressing islet allograft destruction in normal BALB/c and spontaneously-diabetic NOD recipient mice. Transplantation 79, 1104-1109
45. Karlsen, A.e., Ronn, S.G., Lindberg, K., Johannesen, J., Galsgaard, E.D., Pociot, F., Nielsen, J.H., Mandrup-Poulsen, T., Nerup, J. and Billestrup, N. (2001) Suppressor of cytokine signalling-3 (SOCS-3) protects β-cells against interleukin-1β- and interferon-γ-mediated toxicity. Proc. Natl. Acad. Sci. U.S.A. 98, 12191-12196
46. Karlsen, A.E., Heding, P.E., Frobose, H., Ronn, S.G., Kruhoffer, M., Orntoft, T.F., Darville, M., Eizirik, D.L., Pociot, F., Nerup, J. et al. (2004) Suppressor of cytokine signalling (SOCS)-3 protects β-cells against IL-1β-mediated toxicity through inhibition of multiple nuclear factor-κB-regulated proapoptotic pathways. Diabetologia 47, 1998-2011
47. Lindberg, K., Ronn, S.G., Tornehave, D., Richter, H., Hansen, J.A., Romer, J., Jackerott, M. and Billestrup, N. (2005) Regulation of pancreatic β-cell mass and proliferation by SOCS-3. J. Mol. Endocrinol. 35, 231-243
48. Guo, D., Li, M., Zhang, Y., Yang, P., Eckenrode, S., Hopkins, D., Zheng, W., Purohit, S., Podolsky, R.H., Muir, A. et al. (2004) A functional variant of SUMO-4, a new IκBα modifier, is associated with type 1 diabetes. Nat. Genet. 36, 837-841
49. Bohren, K.M., Nadkarni, V., Song, J.H., Gabbay, K.H. and Owerbach, D. (2004) A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J. Biol. Chem. 279, 27233-27238
50. Wang, C.Y. and She, J.X. (2008) SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab. Res. Rev. 24, 93-102
51. Li, M., Guo, D., Isales, C.M., Eizirik, D.L., Atkinson, M., She, J.X. and Wang, C.Y. (2005) SUMO wrestling with type 1 diabetes. J. Mol. Med. 83, 504-513
52. Flodstrom, M. and Eizirik, D.L. (1997) Interferon-γ-induced interferon regulatory factor-1 (IRF-1) expression in rodent and human islet cells precedes nitric oxide production. Endocrinology 138, 2747-2753
53. Karlsen, A.E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H.U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D.L. and Nerup, J. (2000) Interferon-γ induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism. J. Clin. Endocrinol. Metab. 85, 830-836
54. Pavlovic, D., Chen, M.C., Gysemans, C.A., Mathieu, C. and Eizirik, D.L. (1999) The role of interferon regulatory factor-1 in cytokine-induced mRNA expression and cell death in murine pancreatic β-cells. Eur. Cytokine Network 10, 403-412
55. Nakazawa, T., Satoh, J., Takahashi, K., Sakata, Y., Ikehata, F., Takizawa, Y., Bando, S.I., Housai, T., Li, Y., Chen, C. et al. (2001) Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1. J. Autoimmun. 17, 119-125