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Hyperexpression of interferon-gamma-induced mhc class-ii genes associated with reorganization of the cytoskeleton

Academic Article
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Overview

authors

  • Ulevitch, Richard
  • Kline, Lawrence
  • Schreiber, R. D.
  • Pingel, J.
  • Amaldi, I.
  • Reith, W.
  • Mach, B.

publication date

  • August 1991

journal

  • American Journal of Pathology  Journal

abstract

  • Class I and class II major histocompatibility complex (MHC) gene products are key recognition units in the induction and regulation of the immune response. Expression of class I and class II may be constitutive or inducible by cytokines such as interferon-gamma (IFN-gamma). A key step in the induction of MHC genes is recognition of IFN-gamma by its membrane receptor. The work described here examines the regulation of the occupied IFN-gamma receptor by the cytoskeleton. To do this the authors have used the fungal metabolites dihydrocytochalasin B (DHCB) and cytochalasin D (CD), substances that bind to actin filaments and thereby disrupt the cytoskeleton. The authors have studied the effect of DHCB and CD on IFN-gamma-induced MHC gene expression in 143 B cells, a human osteosarcoma-derived cell line. Herein the authors demonstrate that alterations in the cytoskeleton induced by DHCB and CD can lead to increases in IFN-gamma-induced MHC gene expression. Dihydrocytochalasin B added up to 3 hours after IFN-gamma results in a threefold to sixfold increase in levels of class II mRNA while producing minimal enhancement of class I gene expression. In contrast, glyceraldehyde-3-phosphate dehydrogenase mRNA expression was unaltered by IFN-gamma or by the cytochalasins. The increased amount of class II mRNA can be accounted for by a concomitant increase in transcription rate of this gene. Studies using 125I-IFN-gamma demonstrate that the occupied IFN-gamma receptor associates with a Triton X-100 insoluble fraction of 143 B cells and that DHCB and CD markedly inhibit this association. The results described here provide evidence that is consistent with the hypothesis that the activity of the occupied IFN-gamma receptor may be modulated by interactions with the cytoskeleton of the cell. This receptor may be one of a group of plasma membrane receptors that are sensitive to the action of cytochalasins after ligand binding.

subject areas

  • B-Lymphocytes
  • Blotting, Northern
  • Cytochalasin B
  • Cytoskeleton
  • Genes, MHC Class II
  • Humans
  • Interferon-gamma
  • RNA, Messenger
  • Time Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured
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Identity

PubMed Central ID

  • PMC1886081

International Standard Serial Number (ISSN)

  • 0002-9440

PubMed ID

  • 1907805
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Additional Document Info

start page

  • 287

end page

  • 296

volume

  • 139

issue

  • 2

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