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

Raymond E. Eid, Deepak A. Rao, Jing Zhou, Sheng-fu Lo, Hooman Ranjbaran, Amy Gallo, Seth I. Sokol, Steven Pfau, Jordan S. Pober, George Tellides

Research output: Contribution to journalArticle

Abstract

Atherosclerosis is an inflammatory disease in which interferon (IFN)-γ, 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. Circulating IL-17 and IFN-γ 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-γ/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1β, IL-6, and IL-23. Both IL-17 and IFN-γ 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-γ but not IL-17 secretion. Blockade of IFN-γ signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-γ synthesis; production of both cytokines was inhibited by transforming growth factor-β1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-γ producers, and unexpectedly, IL-17/IFN-γ 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-γ to enhance IL-6, CXCL8, and CXCL10 secretion. Our findings demonstrate that IL-17 is produced concomitantly with IFN-γ by coronary artery- infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)1424-1432
Number of pages9
JournalCirculation
Volume119
Issue number10
DOIs
Publication statusPublished - Mar 17 2009
Externally publishedYes

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Keywords

  • Coronary disease
  • Inflammation
  • Interleukins
  • Lymphocytes
  • Muscle
  • Smooth

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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