Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids
| Autor: | Zih Ling Huang, Eileen Jea Chien, Michael I.Ta Huang, Ching Pang Chang, Li Ming Lu, Chau Heng Chien, Shyi-Wu Wang, Der Cherng Tarng, Olivia Ya Hsuan Wang |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Sodium-Hydrogen Exchangers Hydrocortisone Physiology Cell Survival medicine.medical_treatment T cell T-Lymphocytes Clinical Biochemistry Serum albumin Apoptosis Lymphocyte Activation Tritium Dexamethasone Amiloride Young Adult Internal medicine medicine Humans Secretion Cytotoxicity Receptor Cation Transport Proteins Glucocorticoids Immunosuppression Therapy Sodium-Hydrogen Exchanger 1 biology Dose-Response Relationship Drug Genome Human Immunosuppression Cell Biology Hydrogen-Ion Concentration medicine.anatomical_structure Endocrinology biology.protein Interleukin-2 Tetradecanoylphorbol Acetate Interleukin-4 medicine.drug Thymidine |
| Zdroj: | Journal of cellular physiology. 223(3) |
| ISSN: | 1097-4652 |
| Popis: | Glucocorticoids (GCs) have been employed as immunosuppressive agents for many years. However, it is still unclear how GCs instantly uncouple T cells from acute stressful inflammatory. In terms of time scale, the genomic activity of the classic GC receptor cannot fulfill this role under crisis; but a rapid non-genomic response can. In a previous study, intracellular acidification was found to be due to a rapid non-genomic inhibition of Na(+)/H(+)-exchange 1 (NHE1) and this event led to the immunosuppression of T cell proliferation by progesterone. The aim of this study was to examine whether there is a rapid acidification response caused by an inhibition of NHE1 activity and to explore the differential non-genomic effect on immunosuppression of hydrocortisone and dexamethasone. The IC(50) values for NHE1-dependent pH(i) recovery by hydrocortisone and dexamethasone are 250 and 1 nM, respectively. Co-stimulation of GCs with phytohemagglutinin (PHA) is able to inhibit PHA-induced IL-2 secretion, IL-4 secretion, and T-cell proliferation. Furthermore, apoptosis in PHA-activated T cells is not induced by hydrocortisone but by dexamethasone. The mechanism of immunosuppression on proliferation by dexamethasone was found to be different of hydrocortisone and seems to involve cytotoxicity against T cells. Moreover, apoptosis induced by dexamethasone and impermeable dexamethasone-bovine serum albumin suggests that the apoptotic immunosuppression occurs through both the plasma membrane and cytoplasmic sites. The rapid inhibitory responses triggered by GCs would seem to release T cells instantly when an acute stress-related response is needed. Nonetheless, the apoptotic immunosuppression by dexamethasone is attributable to its severe cytotoxicity. |
| Databáze: | OpenAIRE |
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