Publikationsserver der Universitätsbibliothek Marburg
Titel:Selective targeting of immunoproteasome subunit LMP7 prevents colitis-associated carcinogenesis
Autor:Vachharajani, Niyati
Weitere Beteiligte: Višekruna, Alexander (PD Dr.)
Veröffentlicht:2016
URI:https://archiv.ub.uni-marburg.de/diss/z2016/0895
DOI: https://doi.org/10.17192/z2016.0895
URN: urn:nbn:de:hebis:04-z2016-08958
DDC:610 Medizin
Titel (trans.):Gezielte Selektion von Immunoproteasom Untereinheit LMP7 reduziert das Risiko Colitis-assoziierter Karzinogenese (CAC)
Publikationsdatum:2016-12-14
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Colitis-associated Carcinogenesis, Entzündung, CAC, Colon, Kolon, Colitis-assoziierte Karzinogenese, Inflammation

Summary:
Chronic inflammation is a well-known risk factor for the development of colonic tumorigenesis. In this study, we show that the immunoproteasome (iP) subunit LMP7 plays a crucial role in the progression of colitis-associated carcinogenesis (CAC). The activity and function of the iP complex has been extensively studied in the context of MHC class I-coupled antigen presentation, inflammation and infectious diseases. Here we show that the absence of LMP7 exerts a protective effect, since the LMP7-deficient mice fail to develop a full scale of carcinogenesis after CAC induction with AOM/DSS treatment. Our findings demonstrate that LMP7 deficiency results in reduced protein expression of pro-tumorigenic cytokines IL-6 and TNF-α in the colon after AOM/DSS treatment. Additionally, LMP7-deficient mice also exhibit significantly decreased mRNA levels of pro-tumorigenic chemokines CXCL1, CXCL2 and CXCL3, as well as cell adhesion molecule VCAM-1, thus highlighting the role of LMP7 in regulation of these pro-tumorigenic factors. The net result of the lack of pro-tumorigenic cytokines and chemokines is an impaired recruitment and subsequent activity of tumour-associated neutrophils (TANs) in the colonic lamina propria. Furthermore, we show that the absence or pharmacological inhibition of LMP7 and the consequent blockade of NF-κB, abrogated the production IL-17A, which possesses a potent carcinogenic activity in the gut. Moreover, in vivo administration of a selective LMP7 inhibitor „ONX-0914‟ during CAC induction reduced the tumour incidence in wild-type (WT) mice. Taken together, we identify the iP complex as a crucial mediator of inflammation-driven colon carcinogenesis and we also propose LMP7 as a potential therapeutic target for CAC to limit the ongoing tumorigenesis in inflammatory bowel disease (IBD) patients.

Bibliographie / References

  1. De Mita, J.K. , L. Elenich, J. J. Monaco, R. A. Colbert, and T. A. Griffin. 2003. “Β2 Subunit Propeptides Influence Cooperative Proteasome Assembly.” Journal of Biological Chemistry 278 (8): 6153-59.
  2. Müller, S, J. Lory, N. Corazza, G. M. Griffiths, K. Z‟graggen, L. Mazzucchelli, A. Kappeler, and C. Mueller. 1998. “Activated CD4+ and CD8+ Cytotoxic Cells Are Present in Increased Numbers in the Intestinal Mucosa from Patients with Active Inflammatory Bowel Disease.” The American Journal of Pathology 152 (1): 261-68.
  3. Lin, Wan-wan, and Michael Karin. 2007. “A Cytokine-Mediated Link between Innate Immunity , Inflammation , and Cancer.” The Journal of Clinical Investigation 117 (5): 1175-83.
  4. Grivennikov, S. I., K.Wang, D. Mucida, C. Andrew Stewart, B. Schnabl, D.Jauch, K.Taniguchi, et al. 2012. “Adenoma-Linked Barrier Defects and Microbial Products Drive IL-23/IL-17-Mediated Tumour Growth.” Nature 491 (7423): 254-58.
  5. Fearon, Eric R., and Bert Vogelstein. 1990. “A Genetic Model for Colorectal Tumorigenesis” Cell 61: 759-67.
  6. Mizoguchi, Emiko, Manasa Kanneganti, and Mari Mino-Kenudson. 2011. “Animal Models of Colitis-Associated Carcinogenesis.” Journal of Biomedicine and Biotechnology 2011.
  7. Neufert, Clemens, Christoph Becker, and Markus F Neurath. 2007. “An Inducible Mouse Model of Colon Carcinogenesis for the Analysis of Sporadic and Inflammation-Driven Tumor Progression.” Nature Protocols 2 (8): 1998-2004.
  8. Gaffen, Sarah L. 2008. “An Overview of IL-17 Function and Signaling.” Cytokine 43 (3): 402-7.
  9. Krappmann, Daniel, and Claus Scheidereit. 2005. “A Pervasive Role of Ubiquitin Conjugation in Activation and Termination of IkappaB Kinase Pathways.” EMBO Reports 6 (4): 321-26.
  10. Souza, H. S. P., C. J. A. Tortori, M. T. L. Castelo-Branco, A. T. P. Carvalho, V. S. Margallo, C.F.S. Delgado, I. Dines, and C. C. S. Elia. 2005. “Apoptosis in the Intestinal Mucosa of Patients with Inflammatory Bowel Disease: Evidence of Altered Expression of FasL and Perforin Cytotoxic Pathways.” International Journal of Colorectal Disease 20 (3): 277- 86.
  11. Glynne, R., S. H. Powis, S. Beck, A. Kelly, L. A. Kerr, and J. Trowsdale. 1991. “A Proteasome-Related Gene between the Two ABC Transporter Loci in the Class II Region of the Human MHC.” Nature 353: 357-60.
  12. Muchamuel, T., M. Basler, M.A. Aujay, E. Suzuki, K. W. Kalim, C. Lauer, C. Sylvain, et al. 2009. “A Selective Inhibitor of the Immunoproteasome Subunit LMP7 Blocks Cytokine Production and Attenuates Progression of Experimental Arthritis.” Nature Medicine 15 (7): 781-87.
  13. Popivanova B. K., K. Kitamura, Y. Wu, T. Kondo, T. Kagaya, S. Kaneko, M. Oshima, C. Fujii, and N. Mukaida. 2008. “Blocking TNF-α in Mice Reduces Colorectal Carcinogenesis Associated with Chronic Colitis” The Journal of Clinical Investigation 118 (2).
  14. Balkwill, Frances. 2004. “Cancer and the Chemokine Network.” Nature Reviews Cancer 4 (7): 540-50.
  15. Lu, Yong Chen, and Paul F. Robbins. 2015. “Cancer Immunotherapy Targeting Neoantigens.” Seminars in Immunology 28 (1). Elsevier Ltd: 22-27.
  16. Brucklacher-Waldert V., E. J. Carr, M. A. Linterman, and M. Veldhoen. 2014. “Cellular Plasticity of CD4+ T Cells in the Intestine.” Frontiers in Immunology 5 (Oct): 1-12.
  17. Yazdani, R., M. Sharifi, A. S. Shirvan, G. Azizi, and M. Ganjalikhani-Hakemi. 2015. “Characteristics of Innate Lymphoid Cells (ILCs) and Their Role in Immunological Disorders (an Update).” Cellular Immunology 298 (1-2). Elsevier Inc.: 66-76.
  18. Wirtz, S., C.Neufert, B. Weigmann, and M. F. Neurath. 2007. “Chemically Induced Mouse Models of Intestinal Inflammation.” Nature Protocols 2 (3): 541-46.
  19. Balkwill, Frances. 2003. “Chemokine Biology in Cancer.” Seminars in Immunology 15 (1): 49-55.
  20. Philip, Murphy. 2001. “Chemokines and The Molecular Basis of Cancer Metastasis” N Engl J Med 345 (11): 833-35.
  21. Chow, Melvyn T., and Andrew D. Luster. 2014. “Chemokines in Cancer.” Cancer Immunology Research 2 (12): 1125-31.
  22. Landskron, G., M. De La Fuente, P. Thuwajit, C. Thuwajit, and M. A. Hermoso. 2014. “Chronic Inflammation and Cytokines in the Tumor Microenvironment.” Journal of Immunology Research 2014.
  23. Waldner, Maximilian J., and Markus F. Neurath. 2009. “Colitis-Associated Cancer: The Role of T Cells in Tumor Development.” Seminars in Immunopathology 31 (2): 249-56.
  24. Velcich A., W. Yang, J. Heyer, A. Fragale, C. Nicholas et.al., 2002. “Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2” Science Vol 295 Vilchez, David, Isabel Saez, and Andrew Dillin. 2014. “The Role of Protein Clearance Mechanisms in Organismal Ageing and Age-Related Diseases.” Nature Communications 5. Nature Publishing Group: 5659.
  25. Bollrath, Julia, and Fiona M. Powrie. 2013. “Controlling the Frontier: Regulatory T-Cells and Intestinal Homeostasis.” Seminars in Immunology 25 (5). Elsevier Ltd: 352-57.
  26. Rock, K. L., and L Shen. 2005. “Cross-Presentation: Underlying Mechanisms and Role in Immune Surveillance.” Immunol Rev 207: 166-83.
  27. Shang, K., Y. P. Bai, C. Wang, Z. Wang, H. Yu Gu, X. Du, X.Yan Zhou, et al. 2012. “Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic ColitisAssociated Carcinogenesis in Mice.” PLoS ONE 7 (12): 1-12.
  28. Turner, M. D., B. Nedjai, T. Hurst, and D. J. Pennington. 2014. “Cytokines and Chemokines: At the Crossroads of Cell Signalling and Inflammatory Disease.” Biochimica et Biophysica Acta - Molecular Cell Research.
  29. Lowry, W. E., C. Blanpain, J.A. Nowak, G. Guasch, L. Lewis, and E. Fuchs. 2005. “Defining the Impact of Beta-Catenin / Tcf Transactivation on Epithelial Stem Cells.” Genes & Development 19: 1596-1611.
  30. Perše, Martina, and Anton Cerar. 2012. “Dextran Sodium Sulphate Colitis Mouse Model: Traps and Tricks.” Journal of Biomedicine and Biotechnology 2012.
  31. Dietrich D., L. Keller, M. Maak, A. L. Boulesteix, J. R. Siewert, B. Holzmann, and K. P. Janssen. 2010. “Differential Expression of the Chemokines GRO-2, GRO-3, and Interleukin-8 in Colon Cancer and Their Impact on Metastatic Disease and Survival.” International Journal of Colorectal Disease 25 (5): 573-81.
  32. Meira, L., J. M. Bugni, S.L. Green, C. Lee, B. Pong et.al., 2008. “DNA Damage Induced by Chronic Inflammation Contributes to Colon Carcinogenesis in Mice.” The Journal of Clinical Investigation 118 (7): 2516-25.
  33. Pagès, Franck. 2007. “Effector Memory T Cells, Early Metastasis, and Survival in Colorectal Cancer.” The New England Journal of Medicine 2007: 307-8.
  34. West, N. R., S.McCuaig, F.Franchini, and F. Powrie. 2015. “Emerging Cytokine Networks in Colorectal Cancer.” Nature Reviews Immunology 15 (10). Nature Publishing Group: 615-29.
  35. Ebstein, F., P. M. Kloetzel, E. Krüger, and U. Seifert. 2012. “Emerging Roles of Immunoproteasomes beyond MHC Class I Antigen Processing.” Cellular and Molecular Life Sciences 69 (15): 2543-58.
  36. Allport, J. R., H .Ding, T. Collins, M. E. Gerritsen, and F. W. Luscinskas. 1997. “EndothelialDependent Mechanisms Regulate Leukocyte Transmigration: A Process Involving the Proteasome and Disruption of the Vascular Endothelial-Cadherin Complex at Endothelial Cell-to-Cell Junctions.” The Journal of Experimental Medicine 186 (4): 517- 27.
  37. Nenci, A., C. Becker, A. Wullaert, R. Gareus, G. van Loo, Si. Danese, M. Huth, et al. 2007. “Epithelial NEMO Links Innate Immunity to Chronic Intestinal Inflammation.” Nature 446 (7135): 557-61.
  38. Blanpain, Cédric, Valerie Horsley, and Elaine Fuchs. 2007. “Epithelial Stem Cells: Turning over New Leaves.” Cell 128 (3): 445-58.
  39. Valatas, Vassilis, Giorgos Bamias, and George Kolios. 2015. “Experimental Colitis Models: Insights into the Pathogenesis of Inflammatory Bowel Disease and Translational Issues.” European Journal of Pharmacology 759. Elsevier: 253-64.
  40. Blatner, N.R. , M. F. Mulcahy, K. L. Dennis, D. Scholtens, D. J. Bentrem, J. D. Phillips, S. Ham, et al. 2012. “Expression of ROR-γt Marks a Pathogenic Regulatory T Cell Subset in Human Colon Cancer” Sci Transl Med 4 (164): 1-12.
  41. Goldberg, A. L. 2007. “Functions of the Proteasome: From Protein Degradation and Immune Surveillance to Cancer Therapy.” Biochemical Society Transactions 35 (Pt 1): 12-17.
  42. Takahashi, Mami, and Keiji Wakabayashi. 2004. “Gene Mutations and Altered Gene Expression in Azoxymethane-Induced Colon Carcinogenesis in rodents ” Cancer Sci 95 (6): 475-80.
  43. Goel, A., R. M. Xicola, T.Nguyen, B. J. Doyle, R. Vanessa, P. Bandipalliam, J. Reyes, et al. 2011. “Hereditary and Familial Colon Cancer” Gastroenterology 138 (3): 2044-58.
  44. Garrett, Wendy S., Jeffrey I. Gordon, and Laurie H. Glimcher. 2010. “Homeostasis and Inflammation in the Intestine.” Cell 140 (6). Elsevier Inc.: 859-70.
  45. King, R.W., R. J. Deshaies, J. M. Peters, and M.W. Kirschner. 1996. “How Proteolysis Drives the Cell Cycle.” Science 274 (5293): 1652-59.
  46. Heink, S. , D. Ludwig, P.M. Kloetzel, and E. Krüger. 2005. “IFN-Gamma-Induced Immune Adaptation of the Proteasome System Is an Accelerated and Transient Response.” Proceedings of the National Academy of Sciences of the United States of America 102 (26): 9241-46.
  47. Jacque, E., E. Schweighoffer, A.Visekruna, S. Papoutsopoulou, J. Janzen, R.Zillwood, D. M Tarlinton, V. L. J. Tybulewicz, and S. C Ley. 2014. “IKK-Induced NF-κB1 p105 Proteolysis Is Critical for B Cell Antibody Responses to T Cell-Dependent Antigen.” The Journal of Experimental Medicine 211 (10): 2085-2101.
  48. Korn, T., E. Bettelli, M. Oukka, and V. K. Kuchroo. 2009. “IL-17 and Th17 Cells.” Annual Review of Immunology 27 (1): 485-517.
  49. Weaver, C. T., R. D. Hatton, P. R. Mangan, and L. E. Harrington. 2007. “IL-17 Family Cytokines and the Expanding Diversity of Effector T Cell Lineages.” Annual Review of Immunology 25: 821-52.
  50. Coffelt, S. B. , K. Kersten, C. W. Doornebal, J. Weiden, K. Vrijland, C. Hau, N. J. M. Verstegen, et al. 2015. “IL-17-Producing γδ T Cells and Neutrophils Conspire to Promote Breast Cancer Metastasis.” Nature 522 (7556): 345-48.
  51. Grivennikov, S. , E. Karin, J. Terzic, D. Mucida, G. Yi Yu, S. Vallabhapurapu, J. Scheller, et al. 2009. “IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated Cancer.” Cancer Cell 15 (2): 103-13.
  52. Angeles, Arkhjamil, Gabriel Fung, and Honglin Luo. 2012. “Immune and Non-Immune Functions of the Immunoproteasome.” Frontiers in Bioscience (Landmark Edition) 17 (January): 1904-16.
  53. Jacobs, J., E. Smits, F. Lardon, P. Pauwels, and V. Deschoolmeester. 2015. “Immune Checkpoint Modulation in Colorectal Cancer: What‟s New and What to Expect.” Journal of Immunology Research 2015.
  54. Disis, Mary L. 2010. “Immune Regulation of Cancer.” Journal of Clinical Oncology 28 (29): 4531-38.
  55. Dwinell, Michael B., Priscilla A. Johanesen, and Jennifer M. Smith. 2003. “Immunobiology of Epithelial Chemokines in the Intestinal Mucosa.” Surgery 133 (6): 601-7.
  56. Wallace, K. L., L.Zheng, Y. Kanazawa, and D. Q. Shih. 2014. “Immunopathology of Inflammatory Bowel Disease.” World Journal of Gastroenterology : WJG 20 (1): 6-21.
  57. Nussbaum, A. K. , M. P. Rodriguez-Carreno, N. Benning, J. Botten, and J. Lindsay Whitton. 2005. “Immunoproteasome-Deficient Mice Mount Largely Normal CD8+ T Cell Responses to Lymphocytic Choriomeningitis Virus Infection and DNA Vaccination.” Journal of Immunology (Baltimore, Md : 1950) 175 (2): 1153-60.
  58. Strehl, B., T. Joeris, M. Rieger, A.Visekruna, K. Textoris-Taube, S. H. E. Kaufmann, P.M. Kloetzel, U. Kuckelkorn, and U. Steinhoff. 2006. “Immunoproteasomes Are Essential for Clearance of Listeria Monocytogenes in Nonlymphoid Tissues but Not for Induction of Bacteria-Specific CD8+ T Cells.” Journal of Immunology (Baltimore, Md. : 1950) 177 (9): 6238-44.
  59. Ebstein, F., A. Voigt, N. Lange, A. Warnatsch, F. Schröter, T. Prozorovski, U. Kuckelkorn, et al. 2013. “Immunoproteasomes Are Important for Proteostasis in Immune Responses.” Cell 152 (5): 935-37.
  60. Krüger, Elke, and Peter M. Kloetzel. 2012. “Immunoproteasomes at the Interface of Innate and Adaptive Immune Responses: Two Faces of One Enzyme.” Current Opinion in Immunology 24 (1): 77-83.
  61. Seifert, U., L. P. Bialy, F. Ebstein, D. Bech-Otschir, A. Voigt, F. Schröter, T.Prozorovski, et al. 2010. “Immunoproteasomes Preserve Protein Homeostasis upon Interferon-Induced Oxidative Stress.” Cell 142 (4): 613-24..
  62. Yewdell, Jonathan W. 2005. “Immunoproteasomes: Regulating the Regulator.” Proceedings of the National Academy of Sciences 102 (26): 9089-90.
  63. Kalim, K. W., M.Basler, C. J Kirk, and M. Groettrup. 2012. “Immunoproteasome Subunit LMP7 Deficiency and Inhibition Suppresses Th1 and Th17 but Enhances Regulatory T Cell Differentiation.” Journal of Immunology (Baltimore, Md. : 1950) 189 (8): 4182-93.
  64. Ivanov, I. I., K. Atarashi, N. Manel, E. L. Brodie, T. Shima, U. Karaoz, D. Wei, et al. 2009. “Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria.” Cell 139 (3). Elsevier Ltd: 485-98.
  65. Lu, Haitian, Weiming Ouyang, and Chuanshu Huang. 2006. “Inflammation, a Key Event in Cancer Development.” Mol Cancer Res 4 (4): 221-33.
  66. Coussens Lisa M., and Zena Werb. 2002. “Inflammation and Cancer.” Nature 420 (6917): 860-67.
  67. Bromberg, Jacqueline, and Timothy C. Wang. 2009. “Inflammation and Cancer: IL-6 and STAT3 Complete the Link.” Cancer Cell 15 (2). Elsevier Inc.: 79-80.
  68. Terzić, J., S. Grivennikov, E. Karin, and M. Karin. 2010. “Inflammation and Colon Cancer.” Gastroenterology 138 (6): 2101-14.
  69. Grivennikov, Sergei I. 2013. “Inflammation and Colorectal Cancer: Colitis-Associated Neoplasia.” Seminars in Immunopathology 35 (2): 229-44.
  70. Elinav, E. , R. Nowarski, C.A. Thaiss, B. Hu, C. Jin, and R. A. Flavell. 2013. “InflammationInduced Cancer: Crosstalk between Tumours, Immune Cells and Microorganisms.” Nature Reviews. Cancer 13 (11): 759-71.
  71. Ben-Neriah, Yinon, and Michael Karin. 2011. “Inflammation Meets Cancer, with NF-κB as the Matchmaker.” Nature Immunology 12 (8): 715-23.
  72. Kaser, Arthur, Sebastian Zeissig, and Richard S. Blumberg. 2010. “Inflammatory Bowel Disease.” The Annual Review of Immunology 38 (12): 956-61.
  73. Miller, Z., L. Ao, K. Bo Kim, and W. Lee. 2013. “Inhibitors of the Immunoproteasome: Current Status and Future Directions.” Current Pharmaceutical Design 19 (22): 4140-51.
  74. Gajewski, Thomas F, Hans Schreiber, and Yang-Xin Fu. 2013. “Innate and Adaptive Immune Cells in the Tumor Microenvironment.” Nature Immunology 14 (10): 1014-22.
  75. Spits, H., D. Artis, M. Colonna, A. Diefenbach, J. P. Di Santo, G. Eberl, S. Koyasu, et al. 2013. “Innate Lymphoid Cells--a Proposal for Uniform Nomenclature.” Nature Reviews. Immunology 13 (2). Nature Publishing Group: 145-49.
  76. Wojno E.D.T., and David Artis. 2012. “Innate Lymphoid Cells: Balancing Immunity, Inflammation, and Tissue Repair in the Intestine.” Cell Host and Microbe 12 (4). Elsevier Inc.: 445-47.
  77. Buonocore, S., P. P. Ahern, H. H. Uhlig, I. I. Ivanov, D. R. Littman, K. J. Maloy, and F. Powrie . 2010. “Innate Lymphoid Cells Drive Interleukin-23-Dependent Innate Intestinal Pathology: Commentary.” Nature 11 (2). Nature Publishing Group: 79.
  78. Walker, Jennifer A, Jillian L Barlow, and Andrew N J McKenzie. 2013. “Innate Lymphoid Cells-How Did We Miss Them?” Nature Reviews. Immunology 13 (2). Nature Publishing Group: 75-87.
  79. Groettrup, M., S. Khan, K. Schwarz, and G. Schmidtke. 2001. “Interferon-γ Inducible Exchanges of 20S Proteasome Active Site Subunits: Why?” Biochimie 83 (3-4): 367-72.
  80. Moseley, T. A., D. R. Haudenschild, L. Rose, and A. H. Reddi. 2003. “Interleukin-17 Family and IL-17 Receptors.” Cytokine and Growth Factor Reviews 14 (2): 155-74.
  81. Martin, B., K. Hirota, D. J. Cua, B. Stockinger, and M. Veldhoen. 2009. “Interleukin-17- Producing γδ T Cells Selectively Expand in Response to Pathogen Products and Environmental Signals.” Immunity 31 (2). Elsevier Ltd: 321-30.
  82. Wang, K., M. Kyoung Kim, G. DiCaro, J. Wong, S. Shalapour, J. Wan, W. Zhang, et al. 2014. “Interleukin-17 Receptor a Signaling in Transformed Enterocytes Promotes Early Colorectal Tumorigenesis.” Immunity 41 (6): 1052-63..
  83. Waldner, Maximilian J., Sebastian Foersch, and Markus F. Neurath. 2012. “Interleukin-6 - A Key Regulator of Colorectal Cancer Development.” International Journal of Biological Sciences.
  84. Peterson, Lance W, and David Artis. 2014. “Intestinal Epithelial Cells: Regulators of Barrier Function and Immune Homeostasis.” Nature Reviews. Immunology 14 (3). Nature Publishing Group: 141-53.
  85. Taupin, D. R. , K. Kinoshita, and D. K. Podolsky. 2000. “Intestinal Trefoil Factor Confers Colonic Epithelial Resistance to Apoptosis.” Proceedings of the National Academy of Sciences 97 (2): 799-804.
  86. Mudter, J., J. Yu, C. Zufferey, A. Brüstle, S. Wirtz, B. Weigmann, A. Hoffman, et al. 2011. “IRF4 Regulates IL-17A Promoter Activity and Controls ROR-Gt-Dependent Th17 Colitis in Vivo.” Inflammatory Bowel Diseases 17 (6): 1343-58.
  87. Baud, Véronique, and Michael Karin. 2009. “Is NF-kappaB a Good Target for Cancer Therapy? Hopes and Pitfalls.” Nature Reviews. Drug Discovery 8 (1): 33-40.
  88. Fehling, H. J., W. Swat, C. Laplace, R. Kuhn et.al. 1994. “MHC Class I Expression in Mice Lacking the Proteasome Subunit LMP-7,” Science (265).
  89. Okazaki, K, M. Morita, I. Nishimori, S. Sano, M. Toyonaga, Y. Nakazawa, Y. Yamamoto, and Y. Yamamoto. 1993. “Major Histocompatibility Antigen-Restricted Cytotoxicity in Inflammatory Bowel Disease.” Gastroenterology 104 (2): 384-91.
  90. Dahlmann, Burkhardt. 2016. “Mammalian Proteasome Subtypes: Their Diversity in Structure and Function.” Archives of Biochemistry and Biophysics 591. Elsevier Inc: 132-40.
  91. McConkey, David J., and Keyi Zhu. 2008. “Mechanisms of Proteasome Inhibitor Action and Resistance in Cancer.” Drug Resistance Updates 11 (4-5): 164-79.
  92. Kincaid, E. Z. , J. W. Che, I. York, H. Escobar, E.Reyes-Vargas, J. C. Delgado, R.M. Welsh, et al. 2012. “Mice Completely Lacking Immunoproteasomes Show Major Changes in Antigen Presentation.” Nature Immunology 13 (2): 129-35.
  93. Vendramini-Costa, D.B. , and J. E. Carvalho. 2012. “Molecular Link Mechanisms between Inflammation and Cancer.” Current Pharmaceutical Design 18 (26): 3831-52.
  94. Wu, Y., S. Antony, J. L. Meitzler, and J. H. Doroshow. 2014. “Molecular Mechanisms Underlying Chronic Inflammation-Associated Cancers.” Cancer Letters 345 (2). Elsevier Ireland Ltd: 164-73.
  95. Colussi D., G. Brandi, F. Bazzoli, and L. Ricciardiello. 2013. “Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention.” International Journal of Molecular Sciences 14 (8): 16365-85.
  96. Wang, Y., K. Wang, G.C. Han, R.X. Wang, H. Xiao, C.M. Hou, R.F. Guo, et al. 2014. “Neutrophil Infiltration Favors Colitis-Associated Tumorigenesis by Activating the Interleukin-1 (IL-1)/IL-6 Axis.” Mucosal Immunology 7 (5): 1106-15.
  97. Kolaczkowska, Elzbieta, and Paul Kubes. 2013. “Neutrophil Recruitment and Function in Health and Inflammation.” Nature Reviews. Immunology 13 (3). Nature Publishing Group: 159-75.
  98. Sadik, Christian D., Nancy D. Kim, and Andrew D. Luster. 2011. “Neutrophils Cascading Their Way to Inflammation.” Trends in Immunology 32 (10). Elsevier Ltd: 452-60.
  99. Powell, Davalyn R., and Anna Huttenlocher. 2016. “Neutrophils in the Tumor Microenvironment.” Trends in Immunology 37 (1). Elsevier Ltd: 41-52.
  100. Tenesa, Albert, and Malcolm G. Dunlop. 2009. “New Insights into the Aetiology of Colorectal Cancer from Genome-Wide Association Studies.” Nature Reviews. Genetics 10 (6): 353-58.
  101. Karin, Michael. 2009. “NF-kappaB as a Critical Link between Inflammation and Cancer.” Cold Spring Harbor Perspectives in Biology 1 (5): 1-14.
  102. Richmond, Ann. 2002. “NF-Kappa B, Chemokine Gene Transcription and Tumour Growth.” Nature Reviews. Immunology 2 (9): 664-74.
  103. Pasparakis, Manolis. 2008. “IKK/NF-kappaB Signaling in Intestinal Epithelial Cells Controls Immune Homeostasis in the Gut.” Mucosal Immunology (November): S54-57.
  104. Kingsbury, Daniel J., Thomas A. Griffin, and Robert A. Colbert. 2000. “Novel Propeptide Function in 20 S Proteasome Assembly Influences  β Subunit Composition.” Journal of Biological Chemistry 275 (31): 24156-62.
  105. Karin, Michael. 2006. “Nuclear Factor-kB in Cancer Development and Progression.” Nature 441 (7092). Nature Publishing Group: 431-36.
  106. Biswas, Subhra K., Paola Allavena, and Alberto Mantovani. 2013. “Tumor-Associated Macrophages: Functional Diversity, Clinical Significance, and Open Questions.” Seminars in Immunopathology 35 (5): 585-600.
  107. Greten F.R., L. Eckmann, T.F.Greten, J.M. Park et.al. 2004. “IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis Associated Cancer.” Cell 118: 285-96.
  108. Takeuchi, Osamu, and Shizuo Akira. 2010. “Pattern Recognition Receptors and Inflammation.” Cell 140 (6). Elsevier Inc.: 805-20.
  109. Gaczynska, M. , K. L. Rock, T. Spies, and A. L. Goldberg. 1994. “Peptidase Activities of Proteasomes Are Differentially Regulated by the Major Histocompatibility ComplexEncoded Genes for Lmp2 and Lmp7.” Proceedings of the National Academy of Sciences 91 (20): 9213-17.
  110. Kryczek, I., M. Banerjee, P. Cheng, L. Vatan, W. Szeliga, S. Wei, E. Huang, et al. 2009. “Plenary Paper Phenotype , Distribution , Generation , and Functional and Clinical Relevance of Th17 Cells in the Human Tumor Environments.” Blood 114 (6): 1141-50.
  111. Fridlender, Z.G., J. Sun, S. Kim, V. Kapoor, G. Cheng, L. Ling, G. Scott Worthen, and S. M. Albelda. 2009. “Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: „N1‟ versus „N2‟ TAN.” Cancer Cell 16 (3). Elsevier Ltd: 183-94.
  112. Basler, M., M. Dajee, C. Moll, M. Groettrup, and C. J. Kirk. 2010. “Prevention of Experimental Colitis by a Selective Inhibitor of the Immunoproteasome.” Journal of Immunology 185 (1): 634-41.
  113. Baugh, James. M., and Evgeny V. Pilipenko. 2004. “20S Proteasome Differentially Alters Translation of Different mRNAs via the Cleavage of eIF4F and eIF3.” Molecular Cell 16 (4): 575-86.
  114. Visekruna, A., T. Joeris, D. Seidel, A. Kroesen, C. Loddenkemper, M. Zeitz, S. H. E. Kaufmann, R. Schmidt-Ullrich, and U. Steinhoff. 2006. “Proteasome-Mediated Degradation of I κ B α and Processing of p105 in Crohn Disease and Ulcerative Colitis.” The Journal of Clinical Investigation 116 (12): 3195-3203.
  115. Groettrup, Marcus, Christopher J Kirk, and Michael Basler. 2010. “Proteasomes in Immune Cells: More than Peptide Producers?” Nature Reviews. Immunology 10 (1). Nature Publishing Group: 73-78.
  116. Dubiel, W., G. Pratt, K. Ferrell, and M. Rechsteiner. 1992. “Purification of an 11S Regulator of the Multicatalytic Protease.” J Biol Chem 267 (31): 22369-77.
  117. Finley, Daniel. 2009. “Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome.” Annual Review of Biochemistry 78: 477-513.
  118. Rakoff-Nahoum, S., J. Paglino, Fa. Eslami-Varzaneh, S. Edberg, and R. Medzhitov. 2004. “Recognition of Commensal Microflora by Toll-like Receptors Is Required for Intestinal Homeostasis.” Cell 118 (2): 229-41.
  119. Thrower, J. S., L. Hoffman, M. Rechsteiner, and C. M. Pickart. 2000. “Recognition of the Polyubiquitin Proteolytic Signal.” The EMBO Journal 19 (1): 94-102.
  120. Housseau, F., S. Wu, E. C. Wick, H. Fan, X. Wu, N. J. Llosa, K. N. Smith, et al. 2016. “Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis.” Cancer Research 76 (8): 2115-24.
  121. Kanarek, Namaa, and Yinon Ben-Neriah. 2012. “Regulation of NF-kappaB by Ubiquitination and Degradation of the IkappaBs.” Immunological Reviews 246 (1): 77-94.
  122. Toole, Susan M. O., Anthony E. Pegg, and James A. Swenberg. 1993. “Repair of O6 - 4 Methylguanine and O -Methylthymidine in F344 Rat Liver Following Treatment with 1, 2-Dimethylhydrazine and O6-Benzylguanine” Cancer Research 3895-98.
  123. Beyer, Marc , and Joachim L. Schultze. 2006. “Review Article Regulatory T Cells in Cancer.” Blood 108 (3): 804-11.
  124. Hyun, Y.S., D. S.Han, A. Reum Lee, C. S. Eun, J. Youn, and H. Y. Kim. 2012. “Role of IL17A in the Development of Colitis-Associated Cancer.” Carcinogenesis 33 (4): 931-36.
  125. Siveen, K. S., and Girija Kuttan. 2009. “Role of Macrophages in Tumour Progression.” Immunology Letters 123 (2): 97-102.
  126. Pasparakis, Manolis. 2012. “Role of NF-Kappa B in Epithelial Biology.” Immunological Reviews 246: 346-58.
  127. Onizawa, M., T. Nagaishi, T. Kanai, K.-i. Nagano, S. Oshima, Y. Nemoto, a. Yoshioka, et al. 2009. “Signaling Pathway via TNF- /NF-κB in Intestinal Epithelial Cells May Be Directly Involved in Colitis-Associated Carcinogenesis.” AJP: Gastrointestinal and Liver Physiology 296: G850-59.
  128. Baud, Véronique., and Michael Karin. 2001. “Signal Transduction by Tumor Necrosis Factor and Its Relatives.” Trends in Cell Biology 11 (9): 372-77.
  129. Kincaid, E.Z. , S. Murata, K. Tanaka, and K. L. Rock. 2016. “Specialized Proteasome Subunits Have an Essential Role in the Thymic Selection of CD8 + T Cells.” Nature Immunology 17 (May): 1-9.
  130. Coux Olivier , Keiji Tanaka, and Alfred L Goldberg. 1996. “Structure and Functions of the 20S and 26S Proteasomes.” Annual Review of Biochemistry 65: 801-47.
  131. Gaffen, Sarah L. 2009. “Structure and Signalling in the IL-17 Receptor Family.” Nature Reviews. Immunology 9 (8). Nature Publishing Group: 556-67.
  132. Kisselev, Alexei F., and Marcus Groettrup. 2014. “Subunit Specific Inhibitors of Proteasomes and Their Potential for Immunomodulation.” Current Opinion in Chemical Biology 23. Elsevier Ltd: 16-22.
  133. Schmidt, N, E. Gonzalez, A. Visekruna, A. A. Kuhl, C. Loddenkemper, H. Mollenkopf, S. H. Kaufmann, U. Steinhoff, and T. Joeris. 2010. “Targeting the Proteasome: Partial Inhibition of the Proteasome by Bortezomib or Deletion of the Immunosubunit LMP7 Attenuates Experimental Colitis.” Gut 59 (7): 896-906.
  134. Becker, Christoph , Massimo C. Fantini, and Markus F. Neurath. 2006. “TGF-Beta as a T Cell Regulator in Colitis and Colon Cancer.” Cytokine and Growth Factor Reviews 17 (1-2): 97-106.
  135. Becker, C. , M. C. Fantini, C. Schramm, H. A. Lehr, S. Wirtz, A. Nikolaev, J. Burg, et al. 2004. “TGF-β Suppresses Tumor Progression in Colon Cancer by Inhibition of IL-6 Trans-Signaling.” Immunity 21 (4): 491-501.
  136. Littman, Dan R., and Alexander Y. Rudensky. 2010. “Th17 and Regulatory T Cells in Mediating and Restraining Inflammation.” Cell 140 (6). Elsevier Inc.: 845-58.
  137. Ueno, A., A.Ghosh, D. Hung, J. Li, and H. Jijon. 2015. “Th17 Plasticity and Its Changes Associated with Inflammatory Bowel Disease.” World Journal of Gastroenterology 21 (43): 12283-95.
  138. Jurida, L., J. Soelch, M.Bartkuhn, K. Handschick, H. Müller, D. Newel, A. Weber, et al. 2015. “The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65.” Cell Reports 10 (5): 726-39.
  139. van de Wetering, M., El. Sancho, C. Verweij, W. de Lau, I.. Oving, A. Hurlstone, K. van der Horn, et al. 2002. “The β-Catenin/TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells.” Cell 111 (2): 241-50.
  140. Balkwill Frances. R. 2012. “The Chemokine System and Cancer.” Journal of Pathology 226 (2): 148-57.
  141. Eggers, M. , B. Boes-Fabian, T. Ruppert, P. M. Kloetzel, and U. H. Koszinowski. 1995. “The Cleavage Preference of the Proteasome Governs the Yield of Antigenic Peptides.” The Journal of Experimental Medicine 182 (6): 1865-70.
  142. Hoesel, Bastian, and Johannes A Schmid. 2013. “The Complexity of NF-κB Signaling in Inflammation and Cancer.” Molecular Cancer 12 (1). Molecular Cancer: 86.
  143. Brüstle, A., S. Heink, M. Huber, C. Rosenplänter, C. Stadelmann, P. Yu, E. Arpaia, T. W. Mak, T. Kamradt, and M. Lohoff. 2007. “The Development of Inflammatory T(H)-17 Cells Requires Interferon-Regulatory Factor 4.” Nature Immunology 8 (9): 958-66.
  144. Solomon, L., S. Mansor, P. Mallon, Ei. Donnelly, M. Hoper, M. Loughrey, S.Kirk, and K. Gardiner. 2010. “The Dextran Sulphate Sodium (DSS) Model of Colitis: An Overview.” Comparative Clinical Pathology 19 (3): 235-39.
  145. Strober, Warren, Ivan Fuss, and Peter Mannon. 2007. “The Fundamental Basis of Inflammatory Bowel Disease.” Journal of Clinical Investigation 117 (3): 514-21.
  146. Fridman, W. H., F. Pagès, C. Sautès-Fridman, and J. Galon. 2012. “The Immune Contexture in Human Tumours: Impact on Clinical Outcome.” Nature Reviews. Cancer 12 (4). Nature Publishing Group: 298-306.
  147. Dunn, Gavin P., Lloyd J. Old, and Robert D. Schreiber. 2004. “The Immunobiology of Cancer Immunosurveillance and Immunoediting.” Immunity 21 (2): 137-48.
  148. Strober, Warren, Ivan J. Fuss, and Richard S. Blumberg. 2002. “The Immunology of Mucosal Model of Inflammation.” Annual Review of Immunology 20 (1): 495-549.
  149. van Deventer, Sjoerd, and Jacques Neefjes. 2010. “The Immunoproteasome Cleans up after Inflammation.” Cell 142 (4). Elsevier Inc.: 517-18.
  150. Brüstle, A., D. Brenner, C. B. Knobbe, P. A. Lang, C. Virtanen, B. M. Hershenfield, C . Reardon, et al. 2012. “The NF-κB Regulator MALT1 Determines the Encephalitogenic Potential of Th17 Cells.” Journal of Clinical Investigation 122 (12): 4698-4709.
  151. Klotz, L., S. Burgdorf, I. Dani, K. Saijo, J. Flossdorf, S. Hucke, J. Alferink, et al. 2009. “The Nuclear Receptor PPAR Gamma Selectively Inhibits Th17 Differentiation in a T CellIntrinsic Fashion and Suppresses CNS Autoimmunity.” The Journal of Experimental Medicine 206 (10): 2079-89.
  152. von Mikecz, A., M.Chen, T. Rockel, and A. Scharf. 2008. “The Nuclear UbiquitinProteasome System: Visualization of Proteasomes, Protein Aggregates, and Proteolysis in the Cell Nucleus.” Methods in Molecular Biology (Clifton, N.J.) 463.
  153. Ivanov, I. I., B. S. McKenzie, L. Zhou, C. E. Tadokoro, A. Lepelley, J. J. Lafaille, D.J. Cua, and D. R. Littman. 2006. “The Orphan Nuclear Receptor ROR-γt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells.” Cell 126 (6): 1121- 33.
  154. Kloetzel, Peter. M. 2004. “The Proteasome and MHC Class I Antigen Processing.” Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1695 (1-3): 225-33.
  155. Voorhees, Peter M., and Robert Z. Orlowski. 2006. “The Proteasome and Proteasome Inhibitors in Cancer Therapy.” Annual Review of Pharmacology and Toxicology 46 (1): 189-213.
  156. Wolf, Dieter H., and Wolfgang Hilt. 2004. “The Proteasome: A Proteolytic Nanomachine of Cell Regulation and Waste Disposal.” Biochimica et Biophysica Acta - Molecular Cell Research 1695 (1-3): 19-31.
  157. Fricke, B., S. Heink, J.Steffen, P.M. Kloetzel, and E. Krüger. 2007. “The Proteasome Maturation Protein POMP Facilitates Major Steps of 20S Proteasome Formation at the Endoplasmic Reticulum.” EMBO Reports 8 (12): 1170-75.
  158. Baumeister W., J. Walz, F. Zuhl, and E. Seemuller. 1998. “The Proteasome: Paradigm of a Self-Compartmentalizing Protease.” Cell 92 (3): 367-80.
  159. Read, M. A., A. S. Neish, F. W. Luscinskas, Vi. J. Palombella, T. Maniatis, and T. Collins. 1995. “The Proteasome Pathway Is Required for Cytokine-Induced EndothelialLeukocyte Adhesion Molecule Expression.” Immunity.
  160. Joeris, T., N. Schmidt, D. Ermert, P. Krienke, A. Visekruna, U. Kuckelkorn, S. H. E. Kaufmann, and U. Steinhoff. 2012. “The Proteasome System in Infection: Impact of β5 and LMP7 on Composition, Maturation and Quantity of Active Proteasome Complexes.” PLoS ONE 7 (6).
  161. Ye, Jian, Rob S Livergood, and Guangyong Peng. 2013. “The Role and Regulation of Human Th17 Cells in Tumor Immunity.” The American Journal of Pathology 182 (1). American Society for Investigative Pathology: 10-20.
  162. Chen, Jiezhong, and Xu Feng Huang. 2009. “The Signal Pathways in Azoxymethane-Induced Colon Cancer and Preventive Implications.” Cancer Biology and Therapy 8 (14): 1313- 17.
  163. Mudter, J., L. Amoussina, M. Schenk, J.Yu, A. Brüstle, B. Weigmann, R. Atreya, et al. 2008. “The Transcription Factor IFN Regulatory Factor - 4 Controls Experimental Colitis in Mice via T Cell - Derived IL-6.” The Journal of Clinical Investigation 118 (7): 2415-26.
  164. Bonizzi, Giuseppina, and Michael Karin. 2004. “The Two NF-κB Activation Pathways and Their Role in Innate and Adaptive Immunity.” Trends in Immunology 25 (6): 280-88.
  165. Kniepert, Andrea, and Marcus Groettrup. 2014. “The Unique Functions of Tissue-Specific Proteasomes.” Trends in Biochemical Sciences 39 (1). Elsevier Ltd: 17-24.
  166. Visekruna, A., T. Linnerz, V. Martinic, N. Vachharajani, S. Hartmann, H. Harb, T. Joeris, P. I. Pfefferle, M. J. Hofer, and U. Steinhoff. 2015. “Transcription Factor c-Rel Plays a Crucial Role in Driving Anti-CD40-Mediated Innate Colitis.” Mucosal Immunology 8 (2). Nature Publishing Group: 307-15.
  167. Pastille, E., K. Bardini, D. Fleissner, A. Adamczyk, A.Frede, M. Wadwa, D. Von Smolinski, et al. 2014. “Transient Ablation of Regulatory T Cells Improves Antitumor Immunity in Colitis-Associated Colon Cancer.” Cancer Research 74 (16): 4258-69.
  168. Bos, Paula. D. , and Alexander Rudensky. 2012. “Treg Cells in Cancer: A Case of Multiple Personality Disorder.” Sci Transl Med 4 (164): 164fs44.
  169. Galdiero, M. R. , E. Bonavita, I. Barajon, C. Garlanda, A. Mantovani, and S. Jaillon. 2013. “Tumor Associated Macrophages and Neutrophils in Cancer.” Immunobiology 218 (11). Elsevier GmbH.: 1402-10.
  170. Su, X., J. Ye, E. C Hsueh, Y. Zhang, D. F. Hoft, and G. Peng. 2010. “Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells.” Journal of Immunology 184 (3): 1630-41.
  171. Coulie G.P., B. J. Van den Eynde, P. van der Bruggen, and T. Boon. 2014. “Tumour Antigens Recognized by T Lymphocytes: At the Core of Cancer Immunotherapy.” Nature Reviews. Cancer 14 (2). Nature Publishing Group: 135-46.
  172. Ramos, P. C., J. Höckendorff, E. S. Johnson, A. Varshavsky, and R. J. Dohmen. 1998. “Ump1p Is Required for Proper Maturation of the 20S Proteasome and Becomes Its Substrate upon Completion of the Assembly.” Cell 92 (4): 489-99.
  173. Murphy, C. T., G. Moloney, L. J. Hall, A. Quinlan, E. Faivre, P. Casey, F. Shanahan, S. Melgar, and K. Nally. 2010. “Use of Bioluminescence Imaging to Track Neutrophil Migration and Its Inhibition in Experimental Colitis.” Clinical and Experimental Immunology 162 (1): 188-96.
  174. Sánchez-tilló, E., O. De Barrios, L. Siles, M.Cuatrecasas, A. Castells, and A.Postigo. 2011. “ZEB1 to Regulate Tumor Invasiveness.” Proceedings of the National Academy of Sciences (108) no. 48

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