| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294
Astrocytes play a number of important physiological roles in CNS homeostasis. Inflammation stimulates astrocytes to secrete cytokines and chemokines that guide macrophages/microglia and T cells to sites of injury/inflammation. Herein, we describe how these processes are controlled by the suppressor of cytokine signaling (SOCS) proteins, a family of proteins that negatively regulate adaptive and innate immune responses. In this study, we describe that the immunomodulatory cytokine IFN-β induces SOCS-1 and SOCS-3 expression in primary astrocytes at the transcriptional level. SOCS-1 and SOCS-3 transcriptional activity is induced by IFN-β through IFN-
activation site (GAS) elements within their promoters. Studies in STAT-1
-deficient astrocytes indicate that STAT-1 is required for IFN-β-induced SOCS-1 expression, while STAT-3 small interfering RNA studies demonstrate that IFN-β-induced SOCS-3 expression relies on STAT-3 activation. Specific small interfering RNA inhibition of IFN-β-inducible SOCS-1 and SOCS-3 in astrocytes enhances their proinflammatory responses to IFN-β stimulation, such as heightened expression of the chemokines CCL2 (MCP-1), CCL3 (MIP-1), CCL4 (MIP-1β), CCL5 (RANTES), and CXCL10 (IP-10), and promoting chemotaxis of macrophages and CD4+ T cells. These results indicate that IFN-β induces SOCS-1 and SOCS-3 in primary astrocytes to attenuate its own chemokine-related inflammation in the CNS.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health (NIH) Grants NS45290 and NS36765 to E.N.B., a National Multiple Sclerosis Society (NMSS) grant (RG 3892-A-12) to E.N.B. and H.Q., and a NMSS pilot grant (PP1475) to H.Q. B.J.B. is supported by NIH Training Grant T32-NS48039. We acknowledge the support of the University of Alabama at Birmingham Flow Cytometry Core Facility (AM-20614).
2 Address correspondence and reprint requests to Dr. Hongwei Qin, Department of Cell Biology, 1918 University Boulevard, MCLM 392, University of Alabama at Birmingham, Birmingham, AL 35294-0005. E-mail address: hqin{at}uab.edu
3 Abbreviations used in this paper: MS, multiple sclerosis; EAE, experimental autoimmune encephalomyelitis; GAS, IFN- activation site; IRF, IFN regulatory factor; ISGF, interferon-stimulated gene factor; ISRE, IFN-responsive sequence element; RPA, RNase protection assay; RR MS, relapsing-remitting MS; siRNA, small interfering RNA; SOCS, suppressor of cytokine signaling; TKip, tyrosine kinase inhibitor peptide; WT, wild type.
This article has been cited by other articles:
|
|
 |
|
  R. R. Voskuhl, R. S. Peterson, B. Song, Y. Ao, L. B. J. Morales, S. Tiwari-Woodruff, and M. V. Sofroniew Reactive Astrocytes Form Scar-Like Perivascular Barriers to Leukocytes during Adaptive Immune Inflammation of the CNS J. Neurosci., September 16, 2009; 29(37): 11511 - 11522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. DiGiandomenico, L. S. Wylezinski, and J. Hawiger Intracellular Delivery of a Cell-Penetrating SOCS1 that Targets IFN-{gamma} Signaling Sci. Signal., July 21, 2009; 2(80): ra37 - ra37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Qin, L. Wang, T. Feng, C. O. Elson, S. A. Niyongere, S. J. Lee, S. L. Reynolds, C. T. Weaver, K. Roarty, R. Serra, et al. TGF-{beta} Promotes Th17 Cell Development through Inhibition of SOCS3 J. Immunol., July 1, 2009; 183(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
