Novel signal transduction pathways: Analysis of STAT-3 and Rac-1 signaling in inflammatory bowel disease

Annals of the New York Academy of Sciences

Volumn 1072, Issue , 2006, Pages 98-113

  Atreya, R ^a   Atreya, I ^a   Neurath, Markus F ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

Apoptosis; Azathioprine; IL 6R antibody; Inflammatory bowel disease; Signal transduction

Indexed keywords

AZATHIOPRINE; CYTOKINE; GAMMA INTERFERON; GUANOSINE TRIPHOSPHATASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; MERCAPTOPURINE; MESSENGER RNA; MONOCLONAL ANTIBODY; RAC1 PROTEIN; STAT3 PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; CONFERENCE PAPER; CONTROLLED STUDY; CROHN DISEASE; DRUG MECHANISM; DRUG TARGETING; ENTERITIS; ENZYME INHIBITION; INFLAMMATION; INTESTINE; MOUSE; NONHUMAN; SIGNAL TRANSDUCTION;

EID: 33748994835     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1196/annals.1326.001     Document Type: Conference Paper

References (71)

1. PODOLSKY, D.K. 1991. Inflammatory bowel disease. N. Engl. J. Med. 325: 928-937.
2. PODOLSKY, D.K. 2002. Inflammatory bowel disease. N. Engl. J. Med. 347: 417-429.
3. DUCHMANN, R. et al. 1999. Crohn's disease. In Mucosal Immunology. P. L. Ogra, et al., Eds.: 1055-1080. Academic Press, San Diego.
4. FIOCCHI, C. 1998. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115: 182-205.
5. SCHÖLMERICH, J. et al. 1998. Which immunosuppressors do you use to treat Crohn's disease and ulcerative colitis? In which order of priority and how worried are you about toxicity? Inflamm. Bowel Dis. 4: 248-252.
6. SHANAHAN, F. 2002. Crohn's disease. Gastroenterology 120: 622-635.
7. NEURATH, M.F. et al. 2002. The role of Th1/Th2 polarization in mucosal immunity. Nat. Med. 8: 567-573.
8. SARTOR, R.B. 1994. Cytokines in intestinal inflammation: pathophysiologic and clinical considerations. Gastroenterology 106: 533-539.
9. RUTGEERTS, P. et al. 2003. The expanding role of biological agents in the treatment of inflammatory bowel disease-focus on selective adhesion molecule inhibition. Aliment. Pharmacol. Then 17: 1435-1450.
10. INA, K. et al. 1995. Crohn's disease (CD) mucosal T-cells are resistant to apoptosis. Gastroenterology 108: A841.
11. NEURATH, M.F. et al. 2001. Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question. Trends Immunol. 22: 21-26.
12. BOIRIVANT, M. et al. 1999. Lamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis. Gastroenterology 116: 557-565.
13. INA, K. et al. 1999. Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. J. Immunol. 163: 1081-1090.
14. SOUZA, H.S.P. et al. 2005. Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways. Int. J. Colorectal Dis. 20: 277-286.
15. SHANAHAN, F. 2001. Inflammatory bowel disease: immunodiagnostics, immunotherapies, and ecotherapeutics. Gastroenterology 120: 622-635.
16. NEURATH, M.F. et al. 1995. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 182: 1281-1290.
17. Fuss, I.J. et al. 1999. Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. Gastroenterology 117: 1078-1088.
18. MANNON, P.J. et al. 2004. Anti-interleukin-12 antibody for active Crohn's Disease. N. Engl. J. Med. 351: 2069-2079.
19. VAN DEN BRANDE, J.M.H. et al. 2003. Gastroenterology 124: 1774-1785.
20. LUGERING, A. et al. 2001. Infliximab induces apoptosis inmonocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 121: 1145-1157.
21. MITOMA, H. et al. 2005. Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-α. Gastroenterology 128: 376-392.
22. FUSS, I.J. et al. 1996. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J. Immunol. 157: 1261-1270.
23. HOLUB, M.C. et al. 1998. Increased interleukin-6 levels, interleukin-6 receptor and gp130 expression in peripheral lymphocytes of patients with inflammatory bowel disease. Scand. J. Gastroenterol. Supplement 228: 47-50.
24. HYAMS, J.S. et al. 1993. Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease. Gastroenterology 104: 1285-1292.
25. GROSS, V. et al. 1992. Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology 102: 514-519.
26. MAHIDA, Y. et al. 1991. High circulating concentrations of interleukin-6 in active Crohn's disease but not ulcerative colitis. Gut 32: 1531-1534.
27. ISAACS, K.L. et al. 1992. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology 103: 1587-1595.
28. DAIG, R. et al. 2000. Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6. Gut 46: 350-358.
29. REINECKER, H.C. et al. 1993. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin. Exp. Immunol. 94: 174-181.
30. JONES, S.C. et al. 1994. Mucosal interleukin-6 secretion in ulcerative colitis: effects of anti-inflammatory drugs and T-cell stimulation. Scan. J. Gastroenterol. 29: 722-728.
31. REINISCH, W. et al. 1999. Clinical relevance of serum interleukin-6 in Crohn's disease: single point measurements, therapy monitoring, and prediction of clinical relapse. Am. J. Gastroenterol. 94: 2156-2164.
32. ISHIGURO, Y. 1999. Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J. Gastroenterol. 34: 66-74.
33. ATREYA, R. et al. 2000. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn's disease and experimental colitis in vivo. Nat. Med. 6: 583-588.
34. TAGA, T. et al. 1989. Interleukin-6 (IL-6) triggers the association of its receptor (IL-6-R) with a possible signal transducer, gp130. Cell 58: 573-581.
35. HEINRICH, P. et al. 1998. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J. 334: 297-314.
36. HOSOKAWA, T. et al. 1999. Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease. J. Gastroenterol. Hepatol. 14: 987-996.
37. DE JONG, Y.P. et al. 2001. Development of chronic colitis is dependent on the cytokine MIF. Nat. Immunol. 2: 1061-1066.
38. WALEV, I. et al. 1996. Pore-forming toxins trigger shedding of receptors for interleukin 6 and lipopolysaccharide. Proc. Natl. Acad. Sci. USA 93: 7882-7887.
39. MITSUYAMA, K. et al. 1995. Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6. Gut 36: 45-49.
40. HOSOKAWA, T. et al. 1999. Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease. J. Gastroenterol. Hepatol. 14: 987-996.
41. ROSE-JOHN, S. et al. 1994. Soluble receptors for cytokines and growth factors: generation and biological function. Biochem. J. 300: 281-290.
42. ITOH, J. et al. 2001. Decreased bax expression by mucosal T cells favors resistance to apoptosis in Crohn's disease. Gut 49: 35-41.
43. YAMAMOTO, M. et al. 2000. IL-6 is required for the development of TH1 cell-mediated murine colitis. J. Immunol. 164: 4878-4882.
44. ITO, H. et al. 2004. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 126: 989-996.
45. GREENALGH, J.C. et al. 2002. Suppressors of cytokine signaling; relevance to gastrointestinal function and disease. Gastroenterology 123: 2064-2081.
46. MUDTER, J. et al. 2005. Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases. Am. J. Gastroenterol. 100: 64-72.
47. LOVATO, P. et al. 2003. Constitutive activation in intestinal T cells from patients with Crohn's disease. J. Biol. Chem. 278: 16777-16781.
48. WIRTZ, S. et al. 1999. Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF-plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens. J. Immunol. 162: 1884-1488.
49. BAUERLE, P.A., et al. 1997. NF-κB as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol. 65: 111-137.
50. NEURATH, M.F. et al. 1998. Cytokine gene transcription by NF-kappa B family members in patients with inflammatory bowel disease. Ann. N. Y. Acad. Sci. 859: 149-159.
51. NEURATH, M.F. et al. 1996. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat. Med. 9: 998-1004.
52. NEURATH, M.F. et al. 2002. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J. Exp. Med. 195: 1129-1143.
53. PRESENT, D.H. et al. 1980. Treatment of Crohn's disease with 6-mercaptopurine: a long-term, randomized, double-blind study. N. Engl. J. Med. 302: 981-987.
54. LEWIS, J.D., J.S. SCHWARTZ & G.R. LICHTENSTEIN. 2000. Azathioprine for maintenance of remission in Crohn's disease: benefits outweigh the risk of lymphoma. Gastroenterology 118: 1018-1024.
55. FRASE, A.G. et al. 2002. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 50: 485-489.
56. TIEDE, I. et al. 2003. CD28-dependent RacI activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J. Clin. Invest. 111: 1133-1145.
57. CANTRELL, D.A. 2003. GTPases and T cell activation. Immunol. Rev. 192: 122-130.
58. MOVILLA, N. et al. 2001. How Vav proteins discriminate the GtPases Rac1 and RhoA from Cdc42. Oncogene 20: 8057-8065.
59. CRESPO, P. et al. 1997. Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. Nature 385: 169-172.
60. SIMON, A.R. et al. 2000. Regulation of STAT3 by direct binding to the Rac1 GTPase. Science 290: 144-147.
61. FANGER, G.R. et al. 1997. MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42. EMBO J. 16: 4961-4972.
62. KHOSHNAN, A. et al. 2000. The NF-kappa B cascade is important in Bcl-xL expression and for the anti-apoptotic effects of the CD28 receptor in primary human CD4+ lymphocytes. J. Immunol. 165: 1743-1754.
63. GRAD, J.M. et al. 2000. Regulation of Bcl-xL: a little bit of this and a little bit of STAT. Curr. Opin. Oncol. 12: 543-549.
64. PRESENT, D.H. et al. 1980. Treatment of Crohn's disease with 6-mercaptopurine: a long-term, randomized, double-blind study. N. Engl. J. Med. 302: 981-987.
65. CARA, C.J. et al. 2004. Reviewing the mechanism of action of thiopurine drugs: towards a new paradigm in clinical practice. Med. Sci. Monit. 10: RA 247-254.
66. LOWRY, P.W. et al. 2001. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut 49: 665-670.
67. CUFFARI, C. et al. 2001. Utilisation of 6-thioguanine metabolite levels to optimize azathioprine therapy in patients with inflammatory bowel disease. Gut 48: 642-646.
68. SEGAIN, J.P. et al. 2003. Rho kinase blockade prevents inflammation via nuclear factor κB Inhibition: evidence in Crohn's disease and experimental colitis. Gastroenterology 124: 1180-1187.
69. HANAUER, S.B. et al. 2002. Maintenance infliximab for Crohn's disease: the ACCENT 1 randomised trial. Lancet 359: 1541-1549.
70. TARGAN, S.R. et al. 1997. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N. Engl. J. Med. 337: 1029-1035.
71. VAN DULLEMEN, H.M. et al. 1995. Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 109: 129-135.