Enhanced neutrophil autophagy and increased concentrations of IL-6, IL-8, IL-10 and MCP-1 in rheumatoid arthritis

Int Immunopharmacol. 2018 Dec;65:119-128. doi: 10.1016/j.intimp.2018.09.011. Epub 2018 Oct 9.

Abstract

Rheumatoid arthritis (RA) is a high morbidity and disability disease with numerous inflammatory cells infiltrating in interstitial of articular cartilages and bones. As the most abundant inflammatory cells, neutrophil has been reported that their apoptosis changed gradually in the circumstance of RA. Apoptosis, one modality of programmed cell death (PCD), is closely associated with autophagy, which indicates neutrophil autophagy may also alter in RA. Flow cytometry, western blotting, immunohistochemistry, immunofluorescence, transmission electron microscope and multiplex antibody microarray were used to comparative investigate the status of neutrophil autophagy in patients with RA and in vitro. The results showed that the expression of autophagy related LC3 protein was up-regulated with lower lysosomal pH in neutrophils from synovial fluid of RA and changed under stimulation of CQ and small RNA interferences (siRNAs) Atg5 transfection, which proved in acute promyelocytic leukemia HL-60 cell lines, predominantly a neutrophilic promyelocyte, treated by plasma and synovial fluid from RA. We further found out the concentration of IL-6, IL-8, IL-10 and MCP-1 was higher in their synovial fluid which may mediate neutrophil autophagy in RA via cytokine-cytokine receptor interaction and IL-17 signaling pathway. Our results indicate that neutrophil autophagy may be a novel perspective to understand the pathology which may provide a new maker to diagnose RA and IL-8, IL-10, MCP-1 specific antagonists and neutrophil autophagy target inhibitors may improve the therapeutic effect of RA someday.

Keywords: Autophagy; Bioinformatics; Cytokine; Neutrophil; Rheumatoid arthritis.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / metabolism*
  • Autophagy / physiology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Female
  • HL-60 Cells
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Male
  • Microtubule-Associated Proteins
  • Middle Aged
  • Neutrophils / physiology*
  • Synovial Fluid / cytology
  • Up-Regulation

Substances

  • CCL2 protein, human
  • CXCL8 protein, human
  • Chemokine CCL2
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Interleukin-10