Novel signal transduction pathways: analysis of STAT-3 and Rac-1 signaling in inflammatory bowel disease.
Although the precise etiology of inflammatory bowel disease still remains unclear, considerable progress has been made in the identification of novel signal transduction pathways that elucidate the immunopathogenesis involved in the perpetuation of the inflammatory process. Augmented T cell resistance against apoptosis is regarded as a pivotal factor in the pathogenesis, as it impairs mucosal homeostasis and leads to unrestrained accumulation of activated T cells, which subsequently lead to the amplification of the inflammatory response. Therefore novel therapeutic strategies aim at restoring mucosal T cell susceptibility to apoptosis through targeting of signal transduction pathways that are elemental for augmented resistance of T lymphocytes against apoptosis. For example, a newly developed humanized anti-IL-6R monoclonal antibody that induces intestinal T cell apoptosis showed clinical efficacy in patients with active Crohn;s disease. Moreover, recent data that relate the immunosuppressive effects of azathioprine in inflammatory bowel disease to its apoptosis-inducing potential, have important implications for the design of a more specific therapeutic approach. The examination of these novel signal transduction pathways has elucidated the pathogenetic mechanisms involved in inflammatory bowel disease and gives hope for the development of new strategies that may result in a more effective and less toxic therapeutic procedure.
Atreya
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Laboratory of Immunology, Department of Medicine, University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany.
Atreya
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Neurath
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D017209:Apoptosis; D001379:Azathioprine / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D007166:Immunosuppressive Agents; C107953:RAC1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020830:rac1 GTP-Binding Protein; D001379:Azathioprine