| Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids. | |
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MedLine Citation:
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PMID: 20143335 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ching-Pang Chang; Shyi-Wu Wang; Zih-Ling Huang; Olivia Ya-Hsuan Wang; Michael I-Ta Huang; Li-Ming Lu; Der-Cherng Tarng; Chau-Heng Chien; Eileen Jea Chien |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 223 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-07 Completed Date: 2010-04-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 679-86 Citation Subset: IM |
Copyright Information:
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(c) 2010 Wiley-Liss, Inc. |
Affiliation:
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Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Amiloride / analogs & derivatives, pharmacology Apoptosis / drug effects* Cation Transport Proteins / antagonists & inhibitors* Cell Survival / drug effects Dexamethasone / pharmacology* Dose-Response Relationship, Drug Genome, Human / genetics Glucocorticoids / pharmacology* Humans Hydrocortisone / pharmacology* Hydrogen-Ion Concentration / drug effects Immunosuppression* Interleukin-2 / secretion Interleukin-4 / secretion Lymphocyte Activation / drug effects Male Sodium-Hydrogen Antiporter / antagonists & inhibitors* T-Lymphocytes / immunology*, secretion Tetradecanoylphorbol Acetate / pharmacology Thymidine / metabolism Tritium Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Cation Transport Proteins; 0/Glucocorticoids; 0/Interleukin-2; 0/SLC9A1 protein, human; 0/Sodium-Hydrogen Antiporter; 10028-17-8/Tritium; 1214-79-5/5-dimethylamiloride; 16561-29-8/Tetradecanoylphorbol Acetate; 207137-56-2/Interleukin-4; 2609-46-3/Amiloride; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 50-89-5/Thymidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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