Non-genomic rapid inhibition of Na+/H+-exchange 1 and apoptotic immunosuppression in human T cells by glucocorticoids

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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

11 Scopus citations

Abstract

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 IC50 values for NHE1-dependent pHi 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.

Original languageEnglish
Pages (from-to)679-686
Number of pages8
JournalJournal of Cellular Physiology
Volume223
Issue number3
DOIs
StatePublished - 06 2010

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