O-31: Mifepristone Acts as Progesterone Antagonistof Non-Genomic Responses but InhibitsPhytohemagglutinin Induced Proliferationin Human T Cells

Background: Progesterone is an endogenous immunomodulator that suppresses T cell activation during pregnancy. The stimulation of membrane progesterone receptors (mPRs) would seem to be the cause of rapid non-genomic responses in human peripheral T cells, such as an elevation of intracellular calcium ([Ca2+] i) and decreased intracellular pH (pHi). Mifepristoneimmune cells compared with progesterone. We explored whether RU486 is an antagonist to mPRs and can block rapid nongenomic responses and the induction by phytohemagglutinin (PHA) of cell proliferation. Materials and Methods: Human male peripheral T cell responses in terms of pHi and [Ca2+]i changes were measured using the fluorescent dyes, 20,70-bis-(2- carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) and fura-2, respectively. Expression of mPR mRNA was determined by RT–PCR analysis. Cell proliferation and cell toxicity were determined by [3H]-thymidine incorporation and MTT assay, respectively. Results: The mRNAs of mPRa, mPRb and mPRg were expressed in T cells. RU486 blocked progesterone- mediated rapid responses including, the [Ca2+]i increase and pHi decrease, in a dose related manner. RU486 did not block, but enhanced, the inhibitory effect of progesterone on PHA induced cell proliferation. RU486 alone inhibited proliferation induced by PHA and at >25 uM seems to be cytotoxic against resting T cells (p