Expression of IFN-inducible T cell α chemoattractant by human endothelial cells is cyclosporin A-resistant and promotes T cell adhesion:: Implications for cyclosporin A-resistant immune inflammation

被引:26
作者
Mazanet, MM
Neote, K
Hughes, CCW
机构
[1] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA
[2] Pfizer Inc, Groton, CT 06340 USA
关键词
D O I
10.4049/jimmunol.164.10.5383
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IFN-inducible T cell alpha chemoattractant (I-TAC) is a recently discovered member of the CXC chemokine family. It is a potent T cell chemoattractant expressed by IFN-gamma-treated astrocytes, monocytes, keratinocytes, bronchial epithelial cells, and neutrophils. In this study, we show that I-TAG is also expressed by IFN-gamma-treated endothelial cells (EC), both at the mRNA and protein levels. Induction of the I-TAG message is rapid and sustained over 24 h, TNF-alpha does not induce I-TAC mRNA alone,,but does act synergistically with IFN-gamma, Blocking Abs to I-TAG, or to its receptor, CXCR3, reduce T cell adhesion to EC monolayers demonstrating that the expressed protein is functional. Finally, the expression of I-TAG by EC is resistant to the immunosuppressive drug cyclosporin A, suggesting that I-TAG may contribute to the chronic immune inflammation characteristic of graft arteriosclerosis.
引用
收藏
页码:5383 / 5388
页数:6
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