| First Author | Li P | Year | 2011 |
| Journal | Mol Immunol | Volume | 49 |
| Issue | 1-2 | Pages | 64-74 |
| PubMed ID | 21855149 | Mgi Jnum | J:177193 |
| Mgi Id | MGI:5294480 | Doi | 10.1016/j.molimm.2011.07.021 |
| Citation | Li P, et al. (2011) Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: Isoform specific regulation of inflammation. Mol Immunol 49(1-2):64-74 |
| abstractText | Pro-inflammatory cytokines and chemokines play critical roles in autoimmune diseases including rheumatoid arthritis (RA). Recently, it has been reported that beta-arrestin 1 and 2 are involved in the regulation of inflammation. We hypothesized that beta-arrestin 1 and 2 play critical roles in murine models of RA. Using a collagen-induced arthritis (CIA) and a human TNFalpha transgenic (TNFtg) mouse model, we demonstrated that beta-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 beta-arrestin 1 and 2 protein and mRNA levels in the early stage of arthritis. In FLS, low molecular weight hyaluronan (HA)-induced TNFalpha and IL-6 production was increased by overexpression of beta-arrestin 1 but decreased by overexpression of beta-arrestin 2 demonstrating isoform specific regulation. TNFalpha and HA induced an increase of beta-arrestin 1 and 2 expression in FLS, while high mobility group box (HMGB)-1 only stimulated beta-arrestin 1 expression. TNFalpha- or HA-induced beta-arrestin 2 expression was blocked by a p38 inhibitor. To examine the in vivo role of beta-arrestin 2 in the pathogenesis of arthritis, WT and beta-arrestin 2 KO mice were subjected to collagen antibody-induced arthritis (CAIA). beta-Arrestin 2 KO mice exhibited more severe arthritis in CAIA. Thus beta-arrestin 2 is anti-inflammatory in CAIA. These composite observations suggest that beta-arrestin 1 and 2 differentially regulate FLS inflammation and increased beta-arrestin 2 may reduce experimental arthritis severity. |
