In human T cells mifepristone antagonizes glucocorticoid non-genomic rapid responses in terms of Na(+)/H(+)-exchange 1 activity, but not ezrin/radixin/moesin phosphorylation

Steroids
Eileen Jea ChienHsiao-Yi Lin

Abstract

Glucocorticoids (GCs) and progesterone have been employed as immunosuppressive agents during pregnancy for many years. Intracellular acidification by GCs is due to a rapid non-genomic inhibition of membrane Na(+)/H(+)-exchange 1 (NHE1) activity and is followed by immunosuppression of PHA-stimulated proliferation. NHE1 is tethered to the cortical actin cytoskeleton through ezrin/radixin/moesin (ERM) proteins within lipid rafts; these regulate cell shape, migration and resistance to apoptosis. We explored whether mifepristone (RU486), an antagonist of GCs in T cells, is able to completely block rapid non-genomic responses, namely NHE1 activity and the phosphorylation C-terminal residues of ERM proteins at threonine (cp-ERM). GCs stimulate a rapid non-genomic cp-ERM response in cells within 5min. RU486 antagonized the GC-induced rapid decrease in NHE1 activity, and arrested PHA-stimulated T cells at G0/G1 phase but had no effect on the rapid increase in cp-ERM, which persisted for 24h. However, the cp-ERM response was blocked by staurosporine in both resting and GC stimulated cells. The results of RU486 antagonized the GC induced rapid decrease in NHE1 ion transport activity, but not the increase cp-ERM. This suggests that RU486 i...Continue Reading

Citations

Feb 11, 2020·Frontiers in Immunology·Maria Emilia Solano, Petra Clara Arck

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