Direct immunomodulatory influence of IFN-β on human astrocytoma cells

Immunopharmacol Immunotoxicol. 2015 Apr;37(2):214-9. doi: 10.3109/08923973.2015.1014559. Epub 2015 Feb 18.

Abstract

Astrocytes actively play a pivotal role in inflammatory disease intensity of central nervous system especially multiple sclerosis (MS). Although IFN-β is a selective therapy for MS but the role of IFN-β in stimulating the astrocytes to produce cytokines is not clearly revealed. Therefore, it is encouraging to assess the modulatory role of IFN-β on astrocytes of brain tissue. The aim of our study was to analyze the molecular mechanisms of recombinant IFN-β 1a directly affecting IL-10, iNOS, MMP-9 and TIMP-1 expression in central nervous system for the first time. In this way, in vitro procedures conducted by human astrocytoma A172 and 1321N1 cell lines as a model system. The total RNA from A172 and 1321N1 cells treated with IFN-β and LPS/IFN-γ/IFN-β and untreated cells were extracted and evaluated for IL-10, iNOS, MMP-9 and TIMP-1 expression by real-time RT-PCR. We found a significant dose-dependent increase in IL-10 gene expression in A172 and 1321N1 cells treated with IFN-β or LPS/IFN-γ/IFN-β. Moreover, a significant decrease was observed in iNOS expression suggesting a similar mechanism of action for both cells. Eventually there were no significant changes concerning the modulation of the MMP-9 and TIMP-1 in response to IFN-β treatment. In part, the immunomodulatory effect of IFN-β may be due to increase of IL-10 and suppression of iNOS expression in astrocytes of brain tissue.

Keywords: Astrocytoma cells; IFN-β; IL-10; MMP-9; TIMP-1; iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / immunology*
  • Astrocytoma / metabolism*
  • Cell Line, Tumor
  • Humans
  • Immunologic Factors / pharmacology*
  • Interferon-beta / pharmacology*
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / immunology
  • Nitric Oxide Synthase Type II / metabolism

Substances

  • IL10 protein, human
  • Immunologic Factors
  • Interleukin-10
  • Interferon-beta
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II