A Nongenomic Mechanism for Progesterone-mediated Immunosuppression: Inhibition of K+ Channels, Ca2+ Signaling, and Gene Expression in T Lymphocytes
| Autor: | AL Neben, Hubert H. Kerschbaum, PA Negulescu, Cahalan, George R. Ehring, RM Khoury, Christopher M. Fanger, C Eder |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Male
Thapsigargin K+ channel Ovalbumin T cell Placenta T-Lymphocytes Immunology Receptors Antigen T-Cell Gene Expression Biology calcium signaling Progesterone Antagonist Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chloride Channels Pregnancy medicine T lymphocyte Immune Tolerance Potassium Channel Blockers Immunology and Allergy Humans Amino Acid Sequence Maternal-Fetal Exchange Progesterone 030304 developmental biology Calcium signaling 0303 health sciences NFATC Transcription Factors Inward-rectifier potassium ion channel Nuclear Proteins Depolarization Articles Molecular biology Peptide Fragments DNA-Binding Proteins medicine.anatomical_structure chemistry Chloride channel nuclear factor of activated T cells Female Signal transduction 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | The Journal of Experimental Medicine Ehring, GR; Kerschbaum, HH; Eder, C; Neben, AL; Fanger, CM; Khoury, RM; et al.(1998). A nongenomic mechanism for progesterone-mediated immunosuppression: Inhibition of K+ channels, Ca2+ signaling, and gene expression in T lymphocytes. Journal of Experimental Medicine, 188(9), 1593-1602. doi: 10.1084/jem.188.9.1593. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/9vp6q27p |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.188.9.1593. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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