Dextran Sulfate Inhibits IFN-γ-Induced Jak-Stat Pathway in Human Vascular Endothelial Cells
| Autor: | Lawrence A. Hunt, Girish J. Kotwal, Mark A. Wilson, R. H. Lian, David E. Justus |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Immunoprecipitation
Genes MHC Class II Immunology Major histocompatibility complex Interferon-gamma Transactivation Western blot Proto-Oncogene Proteins CIITA medicine Humans STAT1 Phosphorylation biology medicine.diagnostic_test Dextran Sulfate Histocompatibility Antigens Class I JAK-STAT signaling pathway STAT2 Transcription Factor Janus Kinase 2 Protein-Tyrosine Kinases Molecular biology DNA-Binding Proteins STAT1 Transcription Factor Trans-Activators biology.protein Endothelium Vascular |
| Zdroj: | Cellular Immunology. 192:140-148 |
| ISSN: | 0008-8749 |
| DOI: | 10.1006/cimm.1998.1452 |
| Popis: | Human vascular endothelial cells can be induced by IFN-gamma to express class II MHC proteins. Previously, dextran sulfate was shown to selectively inhibit expression of class II MHC by preventing transcription of the gene encoding CIITA, a transactivator protein required for IFN-gamma-inducible expression of class II genes. In this study we characterized the effects of dextran sulfate on the intracellular events occurring prior to CIITA activation. Immunoprecipitation and Western blot analyses indicated that IFN-gamma-induced phosphorylation of Stat1 and Jak2 was blocked by dextran sulfate. In addition, electron micrographs showing the large accumulation of dextran sulfate particles in the cytoplasms of endothelial cells demonstrated that Stat and Jak proteins may directly interact with dextran sulfate. Binding of radiolabeled IFN-gamma to cells indicated that dextran sulfate may also modulate IFN-gamma interactions with the cell surface. Thus, dextran sulfate is capable of interfering with the IFN-gamma-induced expression of class II MHC genes at multiple sites. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect