Protein phosphatase magnesium-dependent 1A induces inflammation in rheumatoid arthritis

Biochem Biophys Res Commun. 2020 Feb 12;522(3):731-735. doi: 10.1016/j.bbrc.2019.11.112. Epub 2019 Nov 30.

Abstract

Rheumatoid arthritis (RA) is a highly inflammatory autoimmune disease. Although proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-6, play a key role in the pathogenesis of RA, the causes of chronic inflammation are not fully understood. Here, we report that protein phosphatase magnesium-dependent 1A (PPM1A) levels were increased in RA synovial fluid compared with osteoarthritis (OA) synovial fluid and positively correlated with TNF levels. In addition, PPM1A expression was increased in synovial tissue from RA patients and joint tissue from a mouse model of arthritis. Finally, extracellular PPM1A induced inflammation by stimulating macrophages to produce TNF through toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88) signaling pathway. Our findings suggest that extracellular PPM1A may contribute to the pathogenesis of RA by functioning as a damage-associated molecular pattern (DAMP) to induce inflammation.

Keywords: DAMP; Inflammation; PPM1A; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Arthritis, Rheumatoid / pathology*
  • Cells, Cultured
  • Female
  • Humans
  • Inflammation / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protein Phosphatase 2C / analysis*
  • RAW 264.7 Cells
  • Synovial Fluid / chemistry
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Tumor Necrosis Factor-alpha
  • PPM1A protein, human
  • Ppm1a protein, mouse
  • Protein Phosphatase 2C