TUMOR-NECROSIS-FACTOR AND IMMUNE INTERFERON SYNERGISTICALLY INCREASE TRANSCRIPTION OF HLA CLASS-I HEAVY-CHAIN AND LIGHT-CHAIN GENES IN VASCULAR ENDOTHELIUM
被引:105
作者:
JOHNSON, DR
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机构:BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115
JOHNSON, DR
POBER, JS
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机构:BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115
POBER, JS
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[1] BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115
Tumor necrosis factor and immune interferon synergistically increase cell-surface expression of class I major histocompatibility complex molecules in cultured human endothelial cells. We report that tumor necrosis factor and interferon γ each independently increase mRNA levels and together cause a greater-than-additive (i.e., synergistic) increase in steady-state mRNA levels and transcriptional rates of the class I heavy- and light-chain genes. HLA heavy-chain mRNA is equally stable in cytokine-treated and -untreated endothelial cells. Interferon γ does not increase tumor necrosis factor receptor number or affinity on human endothelial cells. We conclude that the synergistic increase in class I major histocompatibility complex cell-surface expression results principally from the synergistic increase in transcriptional rates. We propose that this increase is caused by the cooperative binding of independently activated transcription factors to the promoter/enhancer sequences of class I genes.