NDLI: Superantigen-induced steroid resistance depends on activation of phospholipase Cß2.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wildenberg, Manon E. Duijvestein, Marjolijn Löwenberg, Mark Hommes, Daniel W. Peppelenbosch, Maikel P. Van Den Brink, Gijs R. Verhaar, Auke P. Vos, Anne Christine W.
Description	Country affiliation: Netherlands Author Affiliation: Verhaar AP ( Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2300RC Leiden, The Netherlands.)
Abstract	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)Î³-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-PLCÎ³ signaling, superantigens can activate a noncanonical G protein-PLCß-dependent signaling pathway. In this study, we show that staphylococcal enterotoxin B activates a G q and PLCß2-dependent pathway in human T cells. We find that this pathway bypasses the need for canonical Lck-PLCÎ³ signaling in T cell activation and renders superantigen-stimulated T cells insensitive to glucocorticoids in vitro. We show that the PLCß 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Glucocorticoids Pharmacology Lymphocyte Activation Drug Effects Phospholipase C Beta Metabolism Signal Transduction Superantigens Immunology Animals Blotting, Western Dexamethasone Enzyme Activation Immunohistochemistry Immunoprecipitation Lymphocyte Specific Protein Tyrosine Kinase P56(lck) Mice Mice, Inbred C57bl Rna, Small Interfering Receptors, Antigen, T-cell Reverse Transcriptase Polymerase Chain Reaction Transfection Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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