Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice

Tetsuaki Hirase, Hiromitsu Hara, Yoshiyuki Miyazaki, Noriko Ide, Ai Nishimoto-Hazuku, Hirokazu Fujimoto, Christiaan J M Saris, Hiroki Yoshida, Koichi Node

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Chronic inflammation in arterial wall that is driven by immune cells and cytokines plays pivotal roles in the development of atherosclerosis. Interleukin 27 (IL-27) is a member of the IL-12 family of cytokines that consists of IL-27p28 and Epstein-Barr virus induced gene 3 (EBI3) and has anti-inflammatory properties that regulate T cell polarization and cytokine production. IL-27-deficient (Ldlr-/Ebi3-/-) and IL-27 receptor-deficient (Ldlr-/-WSX-1-/-) Ldlr-/- mice were generated and fed with a high-cholesterol diet to induce atherosclerosis. Roles of bone marrow-derived cells in vivo and macrophages in vitro were studied using bone marrow reconstitution by transplantation and cultured peritoneal macrophages, respectively. We demonstrate that mice lacking IL-27 or IL-27 receptor are more susceptible to atherosclerosis compared with wild type due to enhanced accumulation and activation of macrophages in arterial walls. The number of circulating proinflammatory Ly6Chi monocytes showed no significant difference between wild-type mice and mice lacking IL-27 or IL-27 receptor. Administration of IL-27 suppressed the development of atherosclerosis in vivo and macrophage activation in vitro that was indicated by increased uptake of modified low-density lipoprotein and augmented production of proinflammatory cytokines. These findings define a novel inhibitory role for IL-27 in atherosclerosis that regulates macrophage activation in mice.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number3
DOIs
Publication statusPublished - Aug 1 2013
Externally publishedYes

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Interleukin-27
Atherosclerosis
Macrophages
Interleukin Receptors
Macrophage Activation
Cytokines
Arteritis
Peritoneal Macrophages
Interleukin-12
Bone Marrow Transplantation
Human Herpesvirus 4
LDL Lipoproteins
Bone Marrow Cells
Monocytes
Anti-Inflammatory Agents
Cholesterol

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice. / Hirase, Tetsuaki; Hara, Hiromitsu; Miyazaki, Yoshiyuki; Ide, Noriko; Nishimoto-Hazuku, Ai; Fujimoto, Hirokazu; Saris, Christiaan J M; Yoshida, Hiroki; Node, Koichi.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 305, No. 3, 01.08.2013.

Research output: Contribution to journalArticle

Hirase, Tetsuaki ; Hara, Hiromitsu ; Miyazaki, Yoshiyuki ; Ide, Noriko ; Nishimoto-Hazuku, Ai ; Fujimoto, Hirokazu ; Saris, Christiaan J M ; Yoshida, Hiroki ; Node, Koichi. / Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2013 ; Vol. 305, No. 3.
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