Increased interleukin (IL)-20 and IL-24 target osteoblasts and synovial monocytes in spondyloarthritis

Clin Exp Immunol. 2017 Sep;189(3):342-351. doi: 10.1111/cei.12973. Epub 2017 May 2.

Abstract

The pathogenesis of spondyloarthritis (SpA) involves activation of the innate immune system, inflammation and new bone formation. The two cytokines interleukin (IL)-20 and IL-24 have been shown to link innate immune activation and tissue homeostasis. We hypothesized that these two cytokines are secreted as part of activation of the innate immune system and affect bone homeostasis in SpA. IL-20 and IL-24 were measured in plasma from axial SpA patients (n = 83). Peripheral SpA patients (n = 16) were included for in-vitro cell culture studies. The plasma IL-20 and IL-24 levels were increased in SpA patients compared with healthy controls (HCs) by 57 and 83%, respectively (both P < 0·0001). The Toll-like receptor 4-induced secretion of the two cytokines was greater in SpA peripheral blood mononuclear cells (PBMCs) compared with HC PBMCs. IL-20 and IL-24 increased the production of monocyte chemoattractant protein-1 by activated SpA synovial fluid monocytes, decreased the production of Dickkopf-1 by SpA fibroblast-like synovial cells and induced mineralization in human osteoblasts. Taken together, our findings indicate disease-aggravating functions of IL-20 and IL-24 in SpA.

Keywords: Toll-like receptor; interleukin; monocyte; spondylitis.

MeSH terms

  • Adult
  • Calcification, Physiologic / immunology
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / immunology
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukins / blood*
  • Interleukins / immunology*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Monocytes / drug effects
  • Monocytes / immunology
  • Osteoblasts / immunology*
  • Osteoblasts / physiology
  • Spondylarthritis / blood
  • Spondylarthritis / immunology*
  • Spondylarthritis / physiopathology
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukins
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • interleukin-24
  • interleukin 20