Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/53662
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Melino, M. | - |
dc.contributor.author | Hii, C. | - |
dc.contributor.author | McColl, S. | - |
dc.contributor.author | Ferrante, A. | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Journal of Immunology, 2008; 181(10):7300-7306 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.issn | 1550-6606 | - |
dc.identifier.uri | http://hdl.handle.net/2440/53662 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | Michelle Melino, Charles S. Hii, Shaun R. McColl and Antonio Ferrante | - |
dc.language.iso | en | - |
dc.publisher | Amer Assoc Immunologists | - |
dc.source.uri | http://www.jimmunol.org/cgi/content/full/181/10/7300 | - |
dc.subject | T-Lymphocytes | - |
dc.subject | Cells, Cultured | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Mice | - |
dc.subject | MAP Kinase Kinase 4 | - |
dc.subject | Adaptor Proteins, Signal Transducing | - |
dc.subject | Peptide Fragments | - |
dc.subject | Cytokines | - |
dc.subject | Blotting, Western | - |
dc.subject | Lymphocyte Activation | - |
dc.subject | Cell Proliferation | - |
dc.subject | Enzyme Activation | - |
dc.subject | Phosphorylation | - |
dc.subject | tat Gene Products, Human Immunodeficiency Virus | - |
dc.title | The Effect of the JNK Inhibitor, JIP Peptide, on Human T Lymphocyte Proliferation and Cytokine Production | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.4049/jimmunol.181.10.7300 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Hii, C. [0000-0002-7107-8935] | - |
dc.identifier.orcid | McColl, S. [0000-0003-0949-4660] | - |
dc.identifier.orcid | Ferrante, A. [0000-0002-2581-6407] | - |
Appears in Collections: | Aurora harvest 5 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.