The Role of IL-6RA in UHMWPE Promotes Proliferation in Fibro-Like Synovial Cells

Biomed Res Int. 2018 Oct 22:2018:3928915. doi: 10.1155/2018/3928915. eCollection 2018.

Abstract

UHMWPE granule could induce macrophages and inflammatory responses in interfacial tissues, which eliminated the wear debris of UHMWPE component and further induced dissolution of the surrounding bone, leading aseptic loosening. However, the mechanism of synovial cells, especially fibroblast-like synovial (FLS) cells response to UHMWPE, remains unknown. Herein we choose FLS cells as research object. Vimentin (+) CD68 (-) was identified by flow cytometry and immunofluorescent staining assay, and the cells were identified as FLS cells, which was consistent with the experimental requirements. The inhibitory evaluation showed that UHMWPE could significantly promote the proliferation and inhibit apoptosis of FLS cells in dose- and time-dependent manners and increase the levels of proinflammatory cytokines, including IL-6, IL-1β, TNF-α, PGE2, MMP2, and LOX. UHMWPE also can induce the expression of mIL-6R protein in FLS cells and further investigate the relationship between apoptosis and inflammation. Interestingly enough, when we added the interleukin-6 receptor antagonist (IL-6RA), the expression levels of proapoptosis-related proteins increased; in other words, UHMWPE-induced antiapoptosis diminished by IL-6RA (50 μg/ml). Taken together, these findings clearly demonstrated that UHMWPE promote growth in FLS cells through upregulating inflammatory factors to produce antiapoptotic effect.

MeSH terms

  • Cell Proliferation / drug effects*
  • Cytokines / metabolism*
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Polyethylenes / adverse effects
  • Polyethylenes / pharmacology*
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / metabolism*
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology

Substances

  • Cytokines
  • IL6R protein, human
  • Polyethylenes
  • Receptors, Interleukin-6
  • ultra-high molecular weight polyethylene