title: Non-genomic rapid responses via progesterone in human peripheral T cells are not indirectly mimicked by sphingosine 1-phosphate.
abstract: Progesterone is an endogenous immunomodulator that suppresses T cell activation during pregnancy. Progesterone has been shown to induce rapid responses that cause intracellular calcium ([Ca(2+)]i) elevation and acidification followed by inhibition of phytohemagglutinin (PHA)-stimulated proliferation. These rapid responses involve T cell plasma membrane sites, but the mechanisms remain unclear. Three new membrane progesterone receptors (mPRα/mPRβ/mPRγ) have been identified as expressed in T cells. These proteins have been identified as G-protein-coupled receptors. Recently, mPRs have been classified as progestin and adipoQ receptors (PAQRs). Furthermore, they have been suggested to be alkaline ceramidases, possibly involved in mediating sphingolipid signaling. Alkaline ceramidases are capable of converting ceramide to sphingosine, which might then be further phosphorylated sphingosine via sphingosine kinase to sphingosine 1-phosphate (S1P). This pathway could result in progesterone acting indirectly via S1P on membrane sphingosine 1-phosphate receptors (S1PRs) in T cells to induce rapid responses. Therefore, our aim was to investigate whether progesterone rapid responses occur indirectly in T cells via S1P. We found that S1P induces [Ca(2+)]i elevation however there was no change in intracellular pH. This is different from the situation with progesterone: S1P alone does not suppress PHA-stimulated cell proliferation and does not act synergistically with progesterone on the inhibition of PHA-induced cell proliferation. In contrast, S1P at 1μM is able to antagonize the proliferation inhibitory effect of progesterone. Thus the rapid responses that are induced by progesterone in human peripheral T cells probably do not involve indirect signaling via S1P and S1PRs.
authors.affiliation: Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, Sindian District, New Taipei City 23143, Taiwan, ROC.
authors.forename: Jiann-Jong
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, ROC.
authors.forename: David Jia-Qing
authors.initials: DJ
authors.lastname: Lin
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, ROC.
authors.forename: Mark Shui-Yu
authors.initials: MS
authors.lastname: Liu
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, ROC. Electronic address: eileen@ym.edu.tw.
authors.forename: Eileen Jea
authors.initials: EJ
authors.lastname: Chien
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D008246:Lysophospholipids; D010835:Phytohemagglutinins; C060506:sphingosine 1-phosphate; D011374:Progesterone; D013110:Sphingosine; D002118:Calcium
keywords: Membrane steroid receptor; Non genomic; PAQR alkaline ceramidase; Progesterone; Sphingosine 1-phosphate; T-cells