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https://hdl.handle.net/2440/53662
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Type: | Journal article |
Title: | The Effect of the JNK Inhibitor, JIP Peptide, on Human T Lymphocyte Proliferation and Cytokine Production |
Author: | Melino, M. Hii, C. McColl, S. Ferrante, A. |
Citation: | Journal of Immunology, 2008; 181(10):7300-7306 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2008 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Michelle Melino, Charles S. Hii, Shaun R. McColl and Antonio Ferrante |
Abstract: | Although JNK is a potential target for treating chronic inflammatory diseases, its role in T lymphocyte function remains controversial. To overcome some of the previous limitations in addressing this issue we have used the recently described transactivator of transcription-JNK-interacting protein (TAT-JIP) peptide, a specific inhibitor that was derived from the minimal JNK-binding region of the scaffold protein, JNK-interacting protein 1 (JIP-1), coupled to the short cell-permeable HIV TAT sequence. Pretreatment of purified human T lymphocytes with the TAT-JIP peptide inhibited the phosphorylation of endogenous jun activated by PHA-PMA. This was associated with a corresponding inhibition of lymphoproliferation, and of IL-2, IFN-gamma, lymphotoxin, and IL-10 cytokine production. Similar results were also found using mouse splenic T cells. Examination of the specificity of TAT-JIP revealed that although the peptide was more selective than the pharmacological inhibitor, SP600125, it also inhibited cyclin-dependent kinase 2, p70 ribosomal protein S6 kinase, and serum and glucocorticoid-regulated kinase activity. Nevertheless, these data demonstrate for the first time the ability of the TAT-JIP peptide to inhibit the JNK pathway and the phosphorylation of jun in intact cells, thereby preventing the activation of the transcription factor, AP-1, and the production of Th1 and Th2 cytokines. Thus JNK could potentially be a target for the development of drugs for the treatment of autoimmune inflammatory diseases. |
Keywords: | T-Lymphocytes Cells, Cultured Animals Humans Mice MAP Kinase Kinase 4 Adaptor Proteins, Signal Transducing Peptide Fragments Cytokines Blotting, Western Lymphocyte Activation Cell Proliferation Enzyme Activation Phosphorylation tat Gene Products, Human Immunodeficiency Virus |
DOI: | 10.4049/jimmunol.181.10.7300 |
Published version: | http://www.jimmunol.org/cgi/content/full/181/10/7300 |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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