Interleukin 27 is increased in carotid atherosclerosis and promotes NLRP3 inflammasome activation

PLoS One. 2017 Nov 27;12(11):e0188387. doi: 10.1371/journal.pone.0188387. eCollection 2017.

Abstract

Aim: Interleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in vitro.

Methods: Plasma IL-27 was measured by enzyme immunoassay in patients with carotid stenosis (n = 140) and in healthy controls (n = 19). Expression of IL-27 and IL-27R was analyzed by quantitative PCR and immunohistochemistry in plaques from patients and in non-atherosclerotic vessels. THP-1 monocytes, primary monocytes and peripheral blood mononuclear cells (PBMCs) were used to study effects of IL-27 in vitro.

Results: Our main findings were: (i) Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. (ii) Gene expression of IL-27 and IL-27R was significantly elevated in plaques compared to control vessels, and co-localized to macrophages. (iii) In vitro, IL-27 increased NLRP3 inflammasome activation in monocytes with enhanced release of IL-1 β.

Conclusions: We demonstrate increased levels of IL-27 and IL-27R in patients with carotid atherosclerosis. Our in vitro findings suggest an inflammatory role for IL-27, which can possibly be linked to atherosclerotic disease development.

MeSH terms

  • Aged
  • Antigens, CD / metabolism
  • Apyrase / metabolism
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / metabolism*
  • Carotid Artery Diseases / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-27 / blood
  • Interleukin-27 / genetics
  • Interleukin-27 / metabolism*
  • Interleukins / metabolism
  • Lipopolysaccharides
  • Macrophages / metabolism
  • Male
  • Minor Histocompatibility Antigens / metabolism
  • Monocytes / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / genetics

Substances

  • Antigens, CD
  • EBI3 protein, human
  • Inflammasomes
  • Interleukin-1beta
  • Interleukin-27
  • Interleukins
  • Lipopolysaccharides
  • Minor Histocompatibility Antigens
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptors, Cytokine
  • STAT Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Apyrase
  • CD39 antigen

Grants and funding

The authors received no specific funding for this work.