Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes

Academic Article

Abstract

  • 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-γ activation site (GAS) elements within their promoters. Studies in STAT-1α-deficient astrocytes indicate that STAT-1α 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-1α), 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. Copyright © 2008 by The American Association of Immunologists, Inc.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Qin H; Niyongere SA; Sun JL; Baker BJ; Benveniste EN
  • Start Page

  • 3167
  • End Page

  • 3176
  • Volume

  • 181
  • Issue

  • 5