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
POBER, JS
机构
[1] BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02115
关键词
Cytokines; Interferon; β; Major histocompatibility complex; Tumor necrosis factor receptors; β[!sub]2[!/sub]-microglobulin;
D O I
10.1073/pnas.87.13.5183
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:5183 / 5187
页数:5
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