Institute for Environment and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, Japan.
Mod Rheumatol. 2013 Sep;23(5):856-63. doi: 10.1007/s10165-012-0752-4. Epub 2012 Sep 25.
CC motif chemokines are considered to be implicated in the pathogenesis of rheumatoid arthritis (RA) via recruitment of monocytes and lymphocytes. CC motif chemokine ligand 13 (CCL13)/monocyte chemoattractant protein-4 (MCP-4) is postulated to be a potent RA inducer. We conducted a study to more precisely clarify the role of CCL13 in RA pathogenesis.
CCL13 expression was evaluated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining in serum samples and synovial tissues from RA patients. The effects of CCL13 against apoptosis were monitored on cultured synovial fibroblasts. The chemoattractant activity of CCL13 was evaluated by the Boyden chamber assay in monocytes (THP-1 cells) and human umbilical vein endothelial cells (HUVECs).
We found that CCL13 serum level and synovial tissue expression were increased in RA patients. CCL13 had chemoattractant activity for both THP-1 cells and HUVECs. Interestingly, CCL13 expression was positively regulated by tumor necrosis factor-alpha (TNF-α). Furthermore, apoptosis induced by hydrogen peroxide (H2O2) and serum deprivation was inhibited by CCL13 on the cultured synovial fibroblasts.
CCL13 may be associated with disease progression as a result of its antiapoptotic effects, increased macrophage infiltration, and synovial tissue angiogenesis in RA patients.
CC 基序趋化因子被认为通过招募单核细胞和淋巴细胞而参与类风湿关节炎 (RA) 的发病机制。CC 基序趋化因子配体 13 (CCL13)/单核细胞趋化蛋白-4 (MCP-4) 被认为是一种有效的 RA 诱导剂。我们进行了一项研究，以更准确地阐明 CCL13 在 RA 发病机制中的作用。
通过酶联免疫吸附试验 (ELISA) 和免疫组织化学染色评估 RA 患者血清样本和滑膜组织中的 CCL13 表达。在培养的滑膜成纤维细胞上监测 CCL13 对细胞凋亡的影响。通过 Boyden 室测定评估 CCL13 对单核细胞 (THP-1 细胞) 和人脐静脉内皮细胞 (HUVEC) 的趋化活性。
我们发现 RA 患者的 CCL13 血清水平和滑膜组织表达增加。CCL13 对 THP-1 细胞和 HUVEC 具有趋化活性。有趣的是，CCL13 表达受肿瘤坏死因子-α (TNF-α) 的正向调节。此外，CCL13 可抑制过氧化氢 (H2O2) 和血清剥夺诱导的培养滑膜成纤维细胞凋亡。
CCL13 可能通过其抗细胞凋亡作用、增加的巨噬细胞浸润和 RA 患者的滑膜组织血管生成与疾病进展相关。
