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Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells.

Abstract：

BACKGROUND:Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis. METHODS AND RESULTS:Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion. CONCLUSIONS:Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

journal_name

Circulation

journal_title

Circulation

authors

Eid RE,Rao DA,Zhou J,Lo SF,Ranjbaran H,Gallo A,Sokol SI,Pfau S,Pober JS,Tellides G

doi

10.1161/CIRCULATIONAHA.108.827618

subject

Has Abstract

pub_date

2009-03-17 00:00:00

pages

1424-32

issue

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.108.827618

journal_volume

119

pub_type

杂志文章

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Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells.