MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis

被引：97

作者：

Jin, Hye Mi ^{[1
]}

Kim, Tae-Jong ^{[1
]}

Choi, Jung-Ho ^{[1
]}

Kim, Moon-Ju ^{[1
]}

Cho, Young-Nan ^{[1
]}

Nam, Kwang-Il ^{[2
]}

Kee, Seung-Jung ^{[3
]}

Moon, Jang Bae ^{[4
]}

Choi, Seok-Yong ^{[5
]}

Park, Dong-Jin ^{[1
]}

Lee, Shin-Seok ^{[1
]}

Park, Yong-Wook ^{[1
]}

机构：

[1] Chonnam Natl Univ, Med Sch & Hosp, Res Inst Med Sci, Dept Rheumatol, Kwangju 501757, South Korea

[2] Chonnam Natl Univ, Sch Med, Dept Anat, Kwangju 501840, South Korea

[3] Chonnam Natl Univ, Med Sch & Hosp, Dept Lab Med, Kwangju 501757, South Korea

[4] Chonnam Natl Univ, Sch Med, Natl Res Lab Regulat Bone Metab & Dis, Med Res Ctr Gene Regulat, Kwangju 501757, South Korea

[5] Chonnam Natl Univ, Sch Med, Dept Biomed Sci, Kwangju, South Korea

来源：

ARTHRITIS RESEARCH & THERAPY | 2014年 / 16卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

RHEUMATOID-ARTHRITIS; EXPRESSION; MACROPHAGES; INDUCTION; CRYSTALS; MIR-155; ROLES; ALPHA; CELLS; MICE;

D O I：

10.1186/ar4531

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Introduction: Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis. Methods: Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti-SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines. Results: The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-alpha and IL-1 beta. Consistent with in vitro observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice. Conclusions: Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.

引用

页数：9

共 31 条

[1]

Src homology 2 domain-containing inositol-5-phosphatase 1 (SITP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism [J].