Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: isoform specific regulation of inflammation

Mol Immunol. 2011 Oct;49(1-2):64-74. doi: 10.1016/j.molimm.2011.07.021. Epub 2011 Aug 19.


Pro-inflammatory cytokines and chemokines play critical roles in autoimmune diseases including rheumatoid arthritis (RA). Recently, it has been reported that β-arrestin 1 and 2 are involved in the regulation of inflammation. We hypothesized that β-arrestin 1 and 2 play critical roles in murine models of RA. Using a collagen-induced arthritis (CIA) and a human TNFα transgenic (TNFtg) mouse model, we demonstrated that β-arrestin 1 and 2 expression are significantly increased in joint tissue of CIA mice and TNFtg mice. In fibroblast-like synoviocytes (FLS) isolated from hind knee joint of CIA mice, we observed an increase of β-arrestin 1 and 2 protein and mRNA levels in the early stage of arthritis. In FLS, low molecular weight hyaluronan (HA)-induced TNFα and IL-6 production was increased by overexpression of β-arrestin 1 but decreased by overexpression of β-arrestin 2 demonstrating isoform specific regulation. TNFα and HA induced an increase of β-arrestin 1 and 2 expression in FLS, while high mobility group box (HMGB)-1 only stimulated β-arrestin 1 expression. TNFα- or HA-induced β-arrestin 2 expression was blocked by a p38 inhibitor. To examine the in vivo role of β-arrestin 2 in the pathogenesis of arthritis, WT and β-arrestin 2 KO mice were subjected to collagen antibody-induced arthritis (CAIA). β-Arrestin 2 KO mice exhibited more severe arthritis in CAIA. Thus β-arrestin 2 is anti-inflammatory in CAIA. These composite observations suggest that β-arrestin 1 and 2 differentially regulate FLS inflammation and increased β-arrestin 2 may reduce experimental arthritis severity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arrestins / biosynthesis*
  • Arrestins / immunology
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / metabolism*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Blotting, Western
  • Disease Models, Animal
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins


  • ARRB1 protein, human
  • ARRB2 protein, human
  • Arrb1 protein, mouse
  • Arrb2 protein, mouse
  • Arrestins
  • Protein Isoforms
  • Tumor Necrosis Factor-alpha
  • beta-Arrestin 1
  • beta-Arrestin 2
  • beta-Arrestins