Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients

Osteoarthritis Cartilage. 2015 Nov;23(11):1843-52. doi: 10.1016/j.joca.2014.12.007.

Abstract

Objective: Synovitis associated with osteoarthritis (OA) is directly responsible for several clinical symptoms and reflects OA's structural progression. This study sought to analyze the expression of proinflammatory mediations, including Interleukin (IL)-17 and IL-22, which play key roles in regulating inflammatory processes, in inflamed and non-inflamed areas of osteoarthritic synovium.

Methods: Synovium from knees of 32 OA patients were collected at surgery. Macroscopic evaluation of inflammation enabled inflamed and non-inflamed areas to be separated. Samples were incubated to obtain tissue-conditioned media. Quantitative mRNA expression of proinflammatory mediators was analyzed by RT-PCR and protein levels by ELISA and gelatin zymography. Immunohistochemistry and histology were performed.

Results: Inflamed synovium were characterized by increased leukocyte infiltration and a higher vessel-to-tissue area ratio than non-inflamed tissues. Macrophages, T and B lymphocytes, and some neutrophils were found only in the inflamed tissue, and only in the subintimal layer. Levels of proinflammatory cytokines and MMP-9 were significantly higher in tissue-conditioned media from inflamed than non-inflamed tissues. Inflamed areas were associated with higher expression of IL-17 and IL-22, both correlated with the combined release of IL-6, IL-23, and TGFβ1.

Conclusion: Our results showed that inflammatory cytokines, including IL-17 and IL-22, are expressed at higher levels by inflamed OA synovium and suggest IL-22 involvement in OA pathophysiology. This study will help identify new therapeutic strategies for OA, especially the targeting of IL-22 to decrease inflammation.

Keywords: IL-17; IL-22; Osteoarthritis; Synovial inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics*
  • Interleukin-22
  • Interleukins / biosynthesis
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / genetics*
  • Osteoarthritis, Knee / metabolism
  • RNA / genetics*
  • Real-Time Polymerase Chain Reaction
  • Synovial Membrane / metabolism*
  • Synovitis / etiology
  • Synovitis / genetics*
  • Synovitis / metabolism

Substances

  • Interleukin-17
  • Interleukins
  • RNA