Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
复制标题
Interleukin-21 诱导类风湿性关节炎患者成纤维细胞样滑膜细胞的迁移和侵袭
DOI：
10.1111/cei.12751
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发表时间：
2016-05-01
影响因子：
4.6
通讯作者：
Zhao, J.
中科院分区：
文献类型：
--
作者：
Xing, R.;Jin, Y.;Zhao, J.
类风湿性关节炎（RA）是一种以滑膜成纤维细胞增生和骨质侵蚀为特征的慢性炎性疾病。纤维母细胞样滑膜细胞（FLS）通过侵袭性迁移和基质侵袭在RA发病中起关键作用，某些促炎细胞因子可能影响滑膜细胞的侵袭。白介素(IL)-21是否影响这一过程仍有争议。在此，我们评估了IL-21对RA-FLS迁移、侵袭和基质金属蛋白酶（MMP）表达的潜在调节作用。我们发现IL-21促进了RA-FLS的迁移、侵袭和MMP （MMP-2、MMP-3、MMP-9、MMP-13）的产生。此外，IL-21诱导磷酸化肌苷3激酶（PI3K）、信号传导和转录激活因子3 （STAT-3）和细胞外信号调节蛋白激酶1和2 （ERK1/2）通路的激活，阻断这些通路[PI3K/蛋白激酶B （AKT）抑制剂LY294002、STAT-3抑制剂STA-21和ERK1/2抑制剂PD98059]可减弱IL-21诱导的MMP-3和MMP-9的迁移和分泌。总之，我们的研究结果表明IL-21促进了RA-FLS的迁移和侵袭。因此，针对IL-21的治疗策略可能对RA的治疗有效。
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone erosion. Fibroblast-like synoviocytes (FLS) play a pivotal role in RA pathogenesis through aggressive migration and matrix invasion, and certain proinflammatory cytokines may affect synoviocyte invasion. Whether interleukin (IL)-21 influences this process remains controversial. Here, we evaluated the potential regulatory effect of IL-21 on the migration, invasion and matrix metalloproteinase (MMP) expression in RA-FLS. We found that IL-21 promoted the migration, invasion and MMP (MMP-2, MMP-3, MMP-9, MMP-13) production in RA-FLS. Moreover, IL-21 induced activation of the phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways, and blockage of these pathways [PI3K/protein kinase B (AKT) inhibitor LY294002, STAT-3 inhibitor STA-21 and ERK1/2 inhibitor PD98059] attenuated IL-21-induced migration and secretion of MMP-3 and MMP-9. In conclusion, our results suggest that IL-21 promotes migration and invasion of RA-FLS. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.