Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: isoform specific regulation of inflammation.
Increased expression of beta-arrestin 1 and 2 in murine models of rheumatoid arthritis: isoform specific regulation of inflammation.
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DOI：
10.1016/j.molimm.2011.07.021
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Li P;Cook JA;Gilkeson GS;Luttrell LM;Wang L;Borg KT;Halushka PV;Fan H
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.
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DOI：
10.1073/pnas.190276697
发表时间：
2000-09-26
影响因子：
11.1
作者：
DeFea, KA;Vaughn, ZD;Bunnett, NW
通讯作者：
Bunnett, NW
影响因子：
56.9
作者：
Luttrell, LM;Ferguson, SSG;Lefkowitz, RJ
通讯作者：
Lefkowitz, RJ
DOI：
10.1073/pnas.041604898
发表时间：
2001-02-27
影响因子：
11.1
作者：
Luttrell, LM;Roudabush, FL;Lefkowitz, RJ
通讯作者：
Lefkowitz, RJ
影响因子：
4.4
作者：
Joosten, LAB;Koenders, MI;van den Berg, WB
通讯作者：
van den Berg, WB
影响因子：
6.4
作者：
Fan, Hongkuan;Bitto, Alessandra;Cook, James A.
通讯作者：
Cook, James A.