Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase C beta 2
| العنوان: | Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase C beta 2 |
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| المؤلفون: | Daniel W. Hommes, Anne Christine W. Vos, Marjolijn Duijvestein, Maikel P. Peppelenbosch, Auke P. Verhaar, Gijs R. van den Brink, Manon E. Wildenberg, Mark Löwenberg |
| المساهمون: | Gastroenterology & Hepatology, Immunology, Amsterdam institute for Infection and Immunity, Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology |
| المصدر: | Journal of Immunology, 190(12), 6589-6595. American Association of Immunologists Journal of immunology (Baltimore, Md., 190(12), 6589-6595. American Association of Immunologists Journal of Immunology, 190(12), 6589-6595 |
| بيانات النشر: | American Association of Immunologists, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | T cell, Immunology, Blotting, Western, Phospholipase C beta, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, SRC Family Tyrosine Kinase, Lymphocyte Activation, Transfection, Dexamethasone, Enzyme activator, Mice, Glucocorticoid receptor, Superantigen, medicine, Immunology and Allergy, Animals, Humans, Immunoprecipitation, RNA, Small Interfering, Glucocorticoids, Superantigens, biology, Reverse Transcriptase Polymerase Chain Reaction, hemic and immune systems, Immunohistochemistry, Cell biology, Enzyme Activation, Mice, Inbred C57BL, medicine.anatomical_structure, Biochemistry, Gq alpha subunit, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), biology.protein, Female, Signal transduction, Signal Transduction |
| الوصف: | The glucocorticoid receptor is present in a TCR-associated complex, which includes the Src family tyrosine kinase Lck. Glucocorticoids rapidly dissociate this complex, resulting in the inhibition of canonical Lck-phospholipase C (PLC)γ–dependent TCR signaling. The relative importance of this nongenomic role for the glucocorticoid receptor compared with its direct transcriptional effects is not known. Superantigens induce a state of steroid resistance in activated T cells. It was reported that, in addition to canonical Lck-PLCγ signaling, superantigens can activate a noncanonical G protein–PLCβ–dependent signaling pathway. In this study, we show that staphylococcal enterotoxin B activates a Gαq and PLCβ2–dependent pathway in human T cells. We find that this pathway bypasses the need for canonical Lck-PLCγ signaling in T cell activation and renders superantigen-stimulated T cells insensitive to glucocorticoids in vitro. We show that the PLCβ inhibitor U-73122 sensitizes staphylococcal enterotoxin B–treated mice to dexamethasone in vivo. In conclusion, we find that effects of glucocorticoids on TCR-induced T cell proliferation are mainly nongenomic and can be bypassed by the activation of an Lck-independent signaling pathway. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08dfda0ac120439ae181e982f5e964b1Test https://doi.org/10.4049/jimmunol.1202898Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....08dfda0ac120439ae181e982f5e964b1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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