TGF-β suppression of IFN-γ-induced class II MHC gene expression does not involve inhibition of phosphorylation of JAK1, JAK2, or signal transducers and activators of transcription, or modification of IFN-γ enhanced factor X expression

Academic Article

Abstract

  • TGF-β is a widely expressed immunoregulatory protein that exerts a diverse range of effects on many types of cells. One of the effects of TGF- β is the inhibition of both constitutive and cytokine-inducible class II MHC gene expression. In this study, we demonstrate that TGF-β inhibits expression of class II MHC surface protein, mRNA, and promoter activity in primary astrocytes, and that this inhibition is both dose and time dependent. TGF-β does not act to inhibit IFN-γ-induced gene expression in a global fashion, as induction of ICAM-1 and IRF-1 gene expression by IFN-γ is unaffected by treatment with TGF-β. Furthermore, TGF-β does not affect events that are involved in IFN-γ-induced intracellular signaling such as tyrosine phosphorylation of JAK1, JAK2, and STAT1α, nor does it affect IFN- γ induction of the class II X2 box binding protein IFN-γ enhanced factor X. We speculate that TGF-β may be exerting its effects by modulating the expression or function of constitutively expressed factors responsible for regulation of class II MHC gene expression in astrocytes.
  • Published In

    Author List

  • Panek RB; Lee YJ; Benveniste EN
  • Start Page

  • 610
  • End Page

  • 619
  • Volume

  • 154
  • Issue

  • 2