Please use this identifier to cite or link to this item:
|Scopus||Web of Science®||Altmetric|
|Title:||The Effect of the JNK Inhibitor, JIP Peptide, on Human T Lymphocyte Proliferation and Cytokine Production|
|Citation:||Journal of Immunology, 2008; 181(10):7300-7306|
|Publisher:||Amer Assoc Immunologists|
|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|
|Appears in Collections:||Paediatrics publications|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.