Mechanisms for Regulation of Cellular Responsiveness to Human IFN-β1a
作者： Stefan A. Dupont , Susan Goelz , Jaya Goyal , Marie Green
DOI: 10.1089/10799900252952280
关键词:
摘要: Interferons (IFNs) are potent, pleiotropic cytokines, and therefore it is likely that the cell has mechanisms to modulate IFN activity in response excessive or prolonged exposure. To investigate this question, Jurkat T cells were exposed IFN-β1a vitro. The effect of dose frequency treatment on receptor expression, signal transduction pathway, biologic was examined. Results demonstrate at even modest doses (60 IU/ml), surface expression subunit, IFNAR-1, decreased significantly, unresponsive further treatment. More interestingly, after an initial with very low concentrations (<10 when levels remained normal phosphorylation signaling molecules occurred, still refractory After withdrawal IFN, full cellular responsiveness a progressive but surprisingly slow process. Cells retreated 2 days 4 IF...
liebertonline.com参考文章(39)
A.C. Greenlund, M.A. Farrar, B.L. Viviano, R.D. Schreiber, Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). The EMBO Journal. ,vol. 13, pp. 1591- 1600 ,(1994) , 10.1002/J.1460-2075.1994.TB06422.X
Takaho A. Endo, Masaaki Masuhara, Masahiro Yokouchi, Ritsu Suzuki, Hiroshi Sakamoto, Kaoru Mitsui, Akira Matsumoto, Shyu Tanimura, Motoaki Ohtsubo, Hiroyuki Misawa, Tadaaki Miyazaki, Nogueira Leonor, Tadatsugu Taniguchi, Takashi Fujita, Yuzuru Kanakura, Seturo Komiya, Akihiko Yoshimura, A new protein containing an SH2 domain that inhibits JAK kinases Nature. ,vol. 387, pp. 921- 924 ,(1997) , 10.1038/43213
R. Hu, Y. Gan, J. Liu, D. Miller, K.C. Zoon, Evidence for multiple binding sites for several components of human lymphoblastoid interferon-alpha Journal of Biological Chemistry. ,vol. 268, pp. 12591- 12595 ,(1993) , 10.1016/S0021-9258(18)31429-7
Elizabeth Cali Cutrone, Jerome A Langer, Contributions of cloned type I interferon receptor subunits to differential ligand binding
1 FEBS Letters. ,vol. 404, pp. 197- 202 ,(1997) , 10.1016/S0014-5793(97)00129-4
I. Flores, T.M. Mariano, S. Pestka, Human interferon omega (omega) binds to the alpha/beta receptor. Journal of Biological Chemistry. ,vol. 266, pp. 19875- 19877 ,(1991) , 10.1016/S0021-9258(18)54862-6
John Alam, Susan Goelz, Patrice Rioux, James Scaramucci, Wendy Jones, Arthur McAllister, Marilyn Campion, Mark Rogge, Comparative Pharmacokinetics and Pharmacodynamics of Two Recomhinant Human Interferon Beta-la (IFNβ-la) Products Administered Intramuscularly in Healthy Male and Female Volunteers Pharmaceutical Research. ,vol. 14, pp. 546- 549 ,(1997) , 10.1023/A:1012128406432
S. V. Kotenko, L. S. Izotova, O. V. Mirochnitchenko, C. Lee, S. Pestka, The intracellular domain of interferon-alpha receptor 2c (IFN-alphaR2c) chain is responsible for Stat activation. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 96, pp. 5007- 5012 ,(1999) , 10.1073/PNAS.96.9.5007
Robyn Starr, Tracy A. Willson, Elizabeth M. Viney, Leecia J. L. Murray, John R. Rayner, Brendan J. Jenkins, Thomas J. Gonda, Warren S. Alexander, Donald Metcalf, Nicos A. Nicola, Douglas J. Hilton, A family of cytokine-inducible inhibitors of signalling Nature. ,vol. 387, pp. 917- 921 ,(1997) , 10.1038/43206
A Celada, R D Schreiber, Internalization and degradation of receptor-bound interferon-gamma by murine macrophages. Demonstration of receptor recycling. Journal of Immunology. ,vol. 139, pp. 147- 153 ,(1987)
B Cohen, D Novick, S Barak, M Rubinstein, LIGAND-INDUCED ASSOCIATION OF THE TYPE I INTERFERON RECEPTOR COMPONENTS Molecular and Cellular Biology. ,vol. 15, pp. 4208- 4214 ,(1995) , 10.1128/MCB.15.8.4208