Hyperexpression of interferon-gamma-induced MHC class II genes associated with reorganization of the cytoskeleton

R. J. Ulevitch, L. Kline, R. D. Schreiber, J. Pingel, I. Amaldi, W. Reith, B. Mach

Research output: Contribution to journalArticle

6 Scopus citations

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-γ). A key step in the induction of MHC genes is recognition of IFN-γ by its membrane receptor. The work described here examines the regulation of the occupied IFN-γ 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-γ-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-γ-induced MHC gene expression. Dihydrocytochalasin B added up to 3 hours after IFN-γ 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-γ 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-γ demonstrate that the occupied IFN-γ 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-γ 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.

Original languageEnglish
Pages (from-to)287-296
Number of pages10
JournalAmerican Journal of Pathology
Volume139
Issue number2
StatePublished - Jan 1 1991
Externally publishedYes

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