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Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells
François Mach, … , Peter Libby, Andrew D. Luster
François Mach, … , Peter Libby, Andrew D. Luster
Published October 15, 1999
Citation Information: J Clin Invest. 1999;104(8):1041-1050. https://doi.org/10.1172/JCI6993.
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Category: Article

Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells

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Abstract

Activated T lymphocytes accumulate early in atheroma formation and persist at sites of lesion growth and rupture, suggesting that they may play an important role in the pathogenesis of atherosclerosis. Moreover, atherosclerotic lesions contain the Th1-type cytokine IFN-γ, a potentiator of atherosclerosis. The present study demonstrates the differential expression of the 3 IFN-γ–inducible CXC chemokines — IFN-inducible protein 10 (IP-10), monokine induced by IFN-γ (Mig), and IFN-inducible T-cell α chemoattractant (I-TAC) — by atheroma-associated cells, as well as the expression of their receptor, CXCR3, by all T lymphocytes within human atherosclerotic lesions in situ. Atheroma-associated endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages (MØ) all expressed IP-10, whereas Mig and I-TAC were mainly expressed in ECs and MØ, as detected by double immunofluorescence staining. ECs of microvessels within lesions also expressed abundant I-TAC. In vitro experiments supported these results and showed that IL-1β, TNF-α, and CD40 ligand potentiated IP-10 expression from IFN-γ–stimulated ECs. In addition, nitric oxide (NO) treatment decreased IFN-γ induction of IP-10. Our findings suggest that the differential expression of IP-10, Mig, and I-TAC by atheroma-associated cells plays a role in the recruitment and retention of activated T lymphocytes observed within vascular wall lesions during atherogenesis.

Authors

François Mach, Alain Sauty, Albert S. Iarossi, Galina K. Sukhova, Kuldeep Neote, Peter Libby, Andrew D. Luster

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Figure 8

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Secretion of IP-10 protein by human ECs in response to cytokine stimulat...
Secretion of IP-10 protein by human ECs in response to cytokine stimulation. Supernatants from human ECs unstimulated (–) or stimulated for 24 hours with IL-1β (10 ng/mL), TNF-α (50 ng/mL), IFN-γ (100 U/mL), or CD40L (5 μg/mL) were analyzed by ELISA for IP-10 levels. This figure is representative of 3 separate experiments using ECs from different donors. Error bars represent SD from triplicates (*P < 0.0001, **P < 0.005).
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