A nongenomic mechanism for progesterone-mediated immunosuppression: Inhibition of K+ channels, Ca2+ signaling, and gene expression in T lymphocytes

Journal of Experimental Medicine

Volumn 188, Issue 9, 1998, Pages 1593-1602

  Ehring, George R ^a   Kerschbaum, Hubert H ^a,b   Eder, Claudia ^a,c   Neben, Amber L ^a   Fanger, Christopher M ^a   Khoury, Rosana M ^a   Negulescu, Paul A ^a,d   Cahalan, Michael D ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF SALZBURG   (Austria)

^c HUMBOLDT UNIVERSITY   (Germany)

^d Aurora Biosciences Corporation   (United States)

Author keywords

Calcium signaling; Gene expression; K+ channel; Nuclear factor of activated T cells; T lymphocyte

Indexed keywords

ANTIGESTAGEN; CALCIUM CHANNEL; CALCIUM ION; CHARYBDOTOXIN; MIFEPRISTONE; POTASSIUM CHANNEL; POTASSIUM ION; PROGESTERONE; T LYMPHOCYTE RECEPTOR;

ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNE RESPONSE; PLACENTA; PREGNANCY; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION; UTERUS;

AMINO ACID SEQUENCE; CALCIUM SIGNALING; CELL LINE; CHLORIDE CHANNELS; DNA-BINDING PROTEINS; FEMALE; GENE EXPRESSION; HUMANS; IMMUNE TOLERANCE; MALE; MATERNAL-FETAL EXCHANGE; NFATC TRANSCRIPTION FACTORS; NUCLEAR PROTEINS; OVALBUMIN; PEPTIDE FRAGMENTS; PLACENTA; POTASSIUM CHANNEL BLOCKERS; PREGNANCY; PROGESTERONE; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES; TRANSCRIPTION FACTORS;

EID: 0032476689     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.188.9.1593     Document Type: Article

References (55)

1. Stites, D.P., and P.K. Siiteri. 1983. Steroids as immunosuppressants in pregnancy. Immunol. Rev. 75:117-138.
2. Pepe, G.J., and E.D. Albrecht. 1995. Actions of placental and fetal adrenal steroid hormones in primate pregnancy. Endocr. Rev. 16:608-648.
3. Beer, A.E., and J.O. Sio. 1982. Placenta as an immunological barrier. Biol. Reprod. 26:15-27.
4. Gurka, G., and R.E. Rocklin. 1987. Reproductive immunology. JAMA (J. Am. Med. Assoc.). 258:2983-2987.
5. Hunt, J.S. 1994. Immunologically relevant cells in the uterus. Biol. Reprod. 50:461-466.
6. Siiteri, P.K., F. Febres, L.E. Clemens, R.J. Chang, B. Gondos, and D. Stites. 1977. Progesterone and maintenance of pregnancy: is progesterone nature's immunosuppressant? Ann. NY Acad. Sci. 286:384-397.
7. Siiteri, P.K., and D.P. Stites. 1982. Immunologic and endocrine interrelationships in pregnancy. Biol. Reprod. 26:1-14.
8. Clemens, L.E., P.K. Siiteri, and D.P. Stites. 1979. Mechanism of immunosuppression of progesterone on maternal lymphocyte activation during pregnancy. J. Immunol. 122: 1978-1985.
9. Van Voorhis, B.J., D.J. Anderson, and J.A. Hill. 1989. The effects of RU 486 on immune function and steroid-induced immunosuppression in vitro. J. Clin. Endocrinol. Metab. 69: 1195-1199.
10. Monterroso, V.H., and P.J. Hansen. 1993. Regulation of bovine and ovine lymphocyte proliferation by progesterone: modulation by steroid receptor antagonists and physiological status. Acta Endocrinol. 129:532-535.
11. Pavia, C., P.K. Siiteri, J.D. Perlman, and D.P. Stites. 1979. Suppression of murine allogeneic cell interactions by sex hormones. J. Reprod. Immunol. 1:33-38.
12. Crabtree, G.R., and N.A. Clipstone. 1994. Signal transmission between the plasma membrane and nucleus of T lymphocytes. Annu. Rev. Biochem. 63:1045-1083.
13. Negulescu, P.A., N. Shastri, and M.D. Cahalan. 1994. Intracellular calcium dependence of gene expression in single T lymphocytes. Proc. Natl. Acad. Sci. USA. 91:2873-2877.
14. Lewis, R.S., and M.D. Cahalan. 1995. Potassium and calcium channels in lymphocytes. Annu. Rev. Immunol. 13:623-653.
15. 2+ signals and immunosuppression. Nature. 383:837-840.
16. 2+ response amplitude and duration. Nature. 386:855-858.
17. 2+ current in human leukemic T cells. Cell Regul. 1:99-112.
18. 2+ stores. Proc. Natl. Acad. Sci. USA. 90:6295-6299.
19. 2+-ATPase inhibitors. J. Immunol. 152:5226-5240.
20. Phipps, D.J., D.R. Branch, and L.C. Schlichter. 1996. Chloride-channel block inhibits T lymphocyte activation and signalling. Cell. Signalling. 8:141-149.
21. 2+ signaling, and reporter gene expression in antigen-specific mouse T cells. J. Immunol. 159:1628-1638.
22. Chandy, K.G., T.E. DeCoursey, M.D. Cahalan, C. McLaughlin, and S. Gupta. 1984. Voltage-gated potassium channels are required for human T lymphocyte activation. J. Exp. Med. 160:369-385.
23. Lin, C.S., R.C. Boltz, J.T. Blake, M. Nguyen, A. Talento, P.A. Fischer, M.S. Springer, N.H. Sigal, R.S. Slaughter, and M.L. Garcia. 1993. Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation. J. Exp. Med. 177:637-645.
24. Cahalan, M.D., and K.G. Chandy. 1997. Ion channels in the immune system as targets for immunosuppression. Curr. Opin. Biotechnol. 8:749-756.
25. Koo, G.C., J.T. Blake, A. Talento, M. Nguyen, S. Lin, A. Sirotina, K. Shah, K. Mulvany, D.J. Hora, P. Cunningham, et al. 1997. Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo. J. Immunol. 158: 5120-5128.
26. Karttunen, J., and N. Shastri. 1991. Measurement of ligand-induced activation in single viable T cells using the lacZ reporter gene element of the human interleukin 2 enhancer. Proc. Natl. Acad. Sci. USA. 88:3972-3976.
27. b complex to T cells. J. Immunol. 150:2724-2736.
28. Cahalan, M.D., K.G. Chandy, T.E. DeCoursey, and S. Gupta. 1985. A voltage-gated potassium channel in human T lymphocytes. J. Physiol. (Lond.). 358:197-237.
29. Fiering, S.N., M. Roederer, G.P. Nolan, D.R. Micklem, D.R. Parks, and L.A. Herzenberg. 1991. Improved FACS-Gal: flow cytometric analysis and sorting of viable eukaryotic cells expressing reporter gene constructs. Cytometry. 12:291-301.
30. Hamill, O.P., A. Marty, E. Neher, B. Sakmann, and F.J. Sigworth. 1981. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch. Eur. J. Physiol. 391:85-100.
31. Horn, R., and A. Marty. 1988. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J. Gen. Physiol. 92:145-159.
32. 2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260:3440-3450.
33. Thastrup, O., A.P. Dawson, O. Scharff, B. Foder, P.J. Cullen, B.K. Drobak, P.J. Bjerrum, S.B. Christensen, and M.R. Hanley. 1989. Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage. Agents Actions. 27:17-23.
34. Runnebaum, B., H. Runnebaum, I. Stober, and J. Zander. 1975. Progesterone 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone levels in different compartments from the human foeto-placental unit. Acta Endocrinol. 80: 558-568.
35. Runnebaum, B., I. Stober, and J. Zander. 1975. Progesterone, 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone in mother and child at birth. Acta Endocrinol. 80: 569-576.
36. 2+ endoplasmic reticulum-ATPase inhibitor thapsigargin. Eur. J. Immunol. 20:2269-2275.
37. 2+ permeability of unstimulated rat lymphocytes. J. Biol. Chem. 266:10872-10879.
38. + channels in intact human T lymphocytes. Noninvasive measurements of membrane currents, membrane potential, and intracellular calcium. J. Gen. Physiol. 105:765-794.
39. Logsdon, N.J., J. Kang, J.A. Togo, E.P. Christian, and J. Aiyar. 1997. A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J. Biol. Chem. 272:32723-32726.
40. Revelli, A., M. Massobrio, and J. Tesarik. 1998. Nongenomic actions of steroid hormones in reproductive tissues. Endocr. Rev. 19:3-17.
41. Michne, W.F., J.W. Guiles, A.M. Treasurywala, L.A. Castonguay, C.A. Weigelt, B. Oconnor, W.A. Volberg, A.M. Grant, C.C. Chadwick, and D.S. Krafte. 1995. Novel inhibitors of potassium ion channels on human T lymphocytes. J. Med. Chem. 38:1877-1883.
42. Nguyen, A., J.C. Kath, D.C. Hanson, M.S. Biggers, P.C. Canniff, C.B. Donovan, R.J. Mather, M.J. Bruns, H. Rauer, J. Aiyar, et al. 1996. Novel nonpeptide agents potently block the C-type inactivated conformation of Kv1.3 and suppress T cell activation. Mol. Pharmacol. 50:1672-1679.
43. Bielefeldt, K., L. Waite, F.M. Abboud, and J.L. Conklin. 1996. Nongenomic effects of progesterone on human intestinal smooth muscle cells. Am. J. Physiol. 271:G370-G376.
44. Waldegger, S., F. Beisse, H. Apfel, S. Breit, H.A. Kolb, D. Haussinger, and F. Lang. 1995. Electrophysiological effects of progesterone on hepatocytes. Biochim. Biophys. Acta. 1266: 186-190.
45. Breit, S., H. Kolb, H. Apfel, C. Haberland, M. Schmitt, D. Heaussinger, J. Graf, and F. Lang. 1998. Regulation of ion channels in rat hepatocytes. Pflügen Arch. Eur. J. Physiol. 435: 203-210.
46. Wu, F.S., T.T. Gibbs, and D.H. Farb. 1990. Inverse modulation of gamma-aminobutyric acid-and glycine-induced currents by progesterone. Mol. Pharmacol. 37:597-602.
47. Bertrand, D., S. Valera, S. Bertrand, M. Ballivet, and D. Rungger. 1991. Steroids inhibit nicotinic acetylcholine receptors. Neuroreport. 2:277-280.
48. Valera, S., M. Ballivet, and D. Bertrand. 1992. Progesterone modulates a neuronal nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. USA. 89:9949-9953.
49. Bergeron, R., C. de Montigny, and G. Debonnel. 1996. Potentiation of neuronal NMDA response induced by dehydroepiandrosterone and its suppression by progesterone: effects mediated via sigma receptors. J. Neurosci. 16:1193-1202.
50. Foresta, C., M. Rossato, and F. Di Virgilio. 1993. Ion fluxes through the progesterone-activated channel of the sperm plasma membrane. Biochem. J. 294:279-283.
51. 2+ influx and the acrosome reaction in human sperm. Cell. Signalling. 5:531-538.
52. Price, M., S.C. Lee, and C. Deutsch. 1989. Charybdotoxin inhibits proliferation and interleukin 2 production in human peripheral blood lymphocytes. Proc. Natl. Acad. Sci. USA. 86: 10171-10175.
53. Hess, S., M. Oortgiesen, and M.D. Cahalan. 1993. Calcium oscillations in human T and natural killer cells depend upon membrane potential and calcium influx. J. Immunol. 150: 2620-2633.
54. Roussev, R.G., N.G. Higgins, and J.A. McIntyre. 1993. Phenotypic characterization of normal human placental mononuclear cells. J. Reprod. Immunol. 25:15-29.
55. + channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol. Pharmacol. 45:1227-1234.