Expression of IFN-inducible T cell alpha chemoattractant by human endothelial cells is cyclosporin A-resistant and promotes T cell adhesion: implications for cyclosporin A-resistant immune inflammation.
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-TAC is also expressed by IFN-gamma-treated endothelial cells (EC), both at the mRNA and protein levels. Induction of the I-TAC 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-TAC, or to its receptor, CXCR3, reduce T cell adhesion to EC monolayers demonstrating that the expressed protein is functional. Finally, the expression of I-TAC by EC is resistant to the immunosuppressive drug cyclosporin A, suggesting that I-TAC may contribute to the chronic immune inflammation characteristic of graft arteriosclerosis.
Mazanet
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MM
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Neote
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Hughes
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D002196:Capillaries / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002464:Cell Migration Inhibition; D002474:Cell-Free System / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D054371:Chemokine CXCL11; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014471:Umbilical Veins
C515202:CXCL11 protein, human; D054371:Chemokine CXCL11; D019743:Chemokines, CXC; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma