دورية أكاديمية
Immunosuppressive activity of endovanilloids:N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways
| العنوان: | Immunosuppressive activity of endovanilloids:N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways |
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| المؤلفون: | Sancho, Rocío, Macho, Antonio, de La Vega, Laureano, Calzado, Marco A., Fiebich, Bernd L., Appendino, Giovanni, Muñoz, Eduardo |
| المصدر: | Sancho , R , Macho , A , de La Vega , L , Calzado , M A , Fiebich , B L , Appendino , G & Muñoz , E 2004 , ' Immunosuppressive activity of endovanilloids : N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways ' , Journal of Immunology , vol. 172 , no. 4 , pp. 2341-2351 . https://doi.org/10.4049/jimmunol.172.4.2341Test |
| سنة النشر: | 2004 |
| المجموعة: | Discovery - University of Dundee Online Publications |
| مصطلحات موضوعية: | Adult, Arachidonic acids, Calcineurin, Calcineurin inhibitors, Cannabinoid receptor Modulators, DNA-binding proteins, Dopamine, Growth inhibitors, Humans, Immunosuppressive agents, Interleukin-2, Jurkat cells, Lymphocyte activation, MAP kinase kinase 1, Mitogen-activated protein kinase kinases, Mitogen-activated protein kinases, NF-kappa B, NFATC transcription factors, Nuclear proteins, Phosphorylation, Promoter regions, Genetic, Protein subunits, Signal transduction, T-lymphocytes, Transcription factor AP-1, Transcription factor RelA, Transcription factors, Transcriptional activation, Tumor necrosis factor-alpha |
| الوصف: | Endogenous N-acyl dopamines such as N-arachidonoyldopamine (NADA) and N-oleoyldopamine have been recently identified as a new class of brain neurotransmitters sharing endocannabinoid and endovanilloid biological activities. As endocannabinoids show immunomodulatory activity, and T cells play a key role in the onset of several diseases that affect the CNS, we have evaluated the immunosuppressive activity of NADA and N-oleoyldopamine in human T cells, discovering that both compounds are potent inhibitors of early and late events in TCR-mediated T cell activation. Moreover, we found that NADA specifically inhibited both IL-2 and TNF-alpha gene transcription in stimulated Jurkat T cells. To further characterize the inhibitory mechanisms of NADA at the transcriptional level, we examined the DNA binding and transcriptional activities of NF-kappaB, NF-AT, and AP-1 transcription factors in Jurkat cells. We found that NADA inhibited NF-kappaB-dependent transcriptional activity without affecting either degradation of the cytoplasmic NF-kappaB inhibitory protein, IkappaBalpha, or DNA binding activity. However, phosphorylation of the p65/RelA subunit was clearly inhibited by NADA in stimulated cells. In addition, NADA inhibited both binding to DNA and the transcriptional activity of NF-AT and AP-1, as expected from the inhibition of NF-AT1 dephosphorylation and c-Jun N-terminal kinase activation in stimulated T cells. Finally, overexpression of a constitutively active form of calcineurin demonstrated that this phosphatase may represent one of the main targets of NADA. These findings provide new mechanistic insights into the anti-inflammatory activities of NADA and highlight their potential to design novel therapeutic strategies to manage inflammatory diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://discovery.dundee.ac.uk/en/publications/8343f514-2590-43dc-bc49-3bd8c1f91856Test |
| DOI: | 10.4049/jimmunol.172.4.2341 |
| الإتاحة: | https://doi.org/10.4049/jimmunol.172.4.2341Test https://discovery.dundee.ac.uk/en/publications/8343f514-2590-43dc-bc49-3bd8c1f91856Test |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.26743C4F |
| قاعدة البيانات: | BASE |
| DOI: | 10.4049/jimmunol.172.4.2341 |
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