Epigallocatechin-3 Gallate Inhibits STAT-1/JAK2/IRF-1/HLA-DR/HLA-B and Reduces CD8 MKG2D Lymphocytes of Alopecia Areata Patients
| Autor: | Sarah Almaghrabi, Andrew G. Messenger, Fatma N Hamed, Rachid Tazi-Ahnini, Andrew J. G. McDonagh, Youssef Bakri |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis lcsh:Medicine Jurkat cells 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine STAT1 Interferon CD8+ NKG2D+ subset medicine Cytotoxic T cell alopecia areata skin and connective tissue diseases biology integumentary system Chemistry lcsh:R Public Health Environmental and Occupational Health NKG2D Molecular biology body regions HaCaT stomatognathic diseases 030104 developmental biology biology.protein epigallocatechin-3-gallate CD8 Ex vivo medicine.drug |
| Zdroj: | International Journal of Environmental Research and Public Health Volume 15 Issue 12 International Journal of Environmental Research and Public Health, Vol 15, Iss 12, p 2882 (2018) |
| ISSN: | 1660-4601 |
| DOI: | 10.3390/ijerph15122882 |
| Popis: | Background: Alopecia areata (AA) is associated with Interferon- &gamma (IFN-&gamma ) mediated T-lymphocyte dysfunction and increased circulating Interleukine-17 (IL-17) levels. Epigallocatechin-3-gallate (EGCG) specifically inhibits IFN-&gamma pathways and unlike Janus Kinase 1 and 2 (JAK1/JAK2) inhibitors (tofacitinib, ruxolitinib), EGCG is safer, more cost-effective, and is a topically active agent. Our objective is to test the mode of action of EGCG in vitro and ex vivo using HaCat, Jurkat cell lines, and peripheral blood mononuclear cells (PBMCs) of AA patients and healthy controls (HCs), respectively. Methods: distribution of T helper cells (Th1, Th17), and cytotoxic cells (CD8) in PBMCs isolated from 30 AA patients and 30 HCs was investigated by flowcytomterty. In vitro treatment of HaCat and Jurkat cells with 40 &mu m EGCG for 48 h was performed to measure the level of phosphorylation of signal transducer and activator of transcription protein STAT1, and replicated in ex vivo model using PBMCs of AA patients. Results: Interestingly, 40 &mu m EGCG is capable of completely inhibiting phosphorylation of STAT1 after 48 h in HaCat and Jurkat cells and ex vivo in PBMCs of AA patients. Based on QPCR data, the action of EGCG on p-STAT1 seems to be mediated via downregulation of the expression of JAK2 but not JAK1 leading to the inhibition of human leukocyte antigens (HLA-DR and HLA-B) expression probably via IRF-1. On the other hand, AA patients have significantly increased levels of Th1, Th17, and CD8 cells and the production of IFN-&gamma and IL-17 by PBMCs in AA patients was significantly higher compared to HC p = 0.008 and p = 0.006, respectively. Total numbers of CD8+ cells were not significantly different between treated and untreated samples. However, CD8+ cells with positive Natural killer group 2 member D (NKG2D) transmembrane receptor (CD8+ NKG2D+ subset) was significantly reduced when PBMCs were treated with 20 &mu m EGCG for 48 h. Conclusion: These results suggest that EGCG has a synergistic action that inhibits expression of HLA-DR and HLA-B molecules via the IFN-&gamma pathway to maintain immune privilege in HF also it reduces CD8+ NKG2D+ subset. |
| Databáze: | OpenAIRE |
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