|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 188, Number 9, November 2, 1998 1593-1602
By
From the Department of Physiology and Biophysics, University of California, Irvine, California 92697
The mechanism by which progesterone causes localized suppression of the immune response
during pregnancy has remained elusive. Using human T lymphocytes and T cell lines, we show
that progesterone, at concentrations found in the placenta, rapidly and reversibly blocks voltage-gated and calcium-activated K+ channels (KV and KCa, respectively), resulting in depolarization of the membrane potential. As a result, Ca2+ signaling and nuclear factor of activated T
cells (NF-AT)-driven gene expression are inhibited. Progesterone acts distally to the initial
steps of T cell receptor (TCR)-mediated signal transduction, since it blocks sustained Ca2+ signals after thapsigargin stimulation, as well as oscillatory Ca2+ signals, but not the Ca2+ transient
after TCR stimulation. K+ channel blockade by progesterone is specific; other steroid hormones had little or no effect, although the progesterone antagonist RU 486 also blocked KV
and KCa channels. Progesterone effectively blocked a broad spectrum of K+ channels, reducing
both Kv1.3 and charybdotoxin-resistant components of KV current and KCa current in T cells,
as well as blocking several cloned KV channels expressed in cell lines. Progesterone had little or
no effect on a cloned voltage-gated Na+ channel, an inward rectifier K+ channel, or on lymphocyte Ca2+ and Cl
channels. We propose that direct inhibition of K+ channels in T cells by
progesterone contributes to progesterone-induced immunosuppression.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
