Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis
Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis
复制标题
活化的巨噬细胞样滑膜细胞对抗原诱导的关节炎中内质网应激诱导的细胞凋亡具有抵抗力
DOI：
10.1007/s00011-013-0705-1
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发表时间：
2014-05-01
影响因子：
6.7
通讯作者：
Shen, Yu-Xian
中科院分区：
文献类型：
--
作者：
Feng, Li-Jie;Jiang, Tong-Cui;Shen, Yu-Xian
目的探讨内质网（endoplasmic reticulum，ER）应激蛋白在抗原诱导性关节炎（antigen induced arthritis，AA）模型中的特征性表达及其在关节炎中的作用。通过磁共振成像和组织学分析评估病理变化。免疫荧光双标法检测滑膜和腹腔巨噬细胞（PMΦ）ER应激蛋白的表达和定位。RT-PCR检测ER应激相关基因mRNA的表达。结果ER应激标志物BiP在关节炎滑膜中表达上调，并广泛表达于成纤维细胞样滑膜细胞（FLS）和巨噬细胞样滑膜细胞（MLS）。促凋亡因子CHOP/GADD 153在炎症滑膜中表达轻度升高，主要定位于FLS，而在MLS中表达不明显。出乎意料的是，在关节炎大鼠的PMΦ中观察到CHOP表达增加。同样，切割的caspase-3很少在MLS中表达。此外，衣霉素诱导的ER应激可导致炎症FLS中IL-1β和TNF-α等促炎分子的表达显著增加。结论滑膜MLS中ER应激蛋白的差异活化可能参与了滑膜细胞抵抗ER应激诱导的凋亡。此外，内质网应激是关节炎炎症的潜在介质。
ObjectiveTo explore the characteristic expression of endoplasmic reticulum (ER) stress protein in antigen-induced arthritis models and the role of ER stress in arthritis.MethodsEffective animal models of rheumatoid arthritis in rabbits and rats were induced by methylated bovine serum albumin and Freund’s complete adjuvant. Pathological changes were assessed by magnetic resonance imaging and histological analysis. The expression and localization of ER stress proteins in synovium and peritoneal macrophages (PMΦ) were analyzed by double immunofluorescence staining. RT-PCR was performed to detect mRNA expression of ER stress-related genes. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in synoviocytes were measured by RT-PCR and radioimmunoassay.ResultsWe found that the ER stress marker BiP was highly up-regulated in arthritis synovium and extensively expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS). The expression of the pro-apoptotic factor CHOP/GADD153 was slightly elevated in inflammatory synovium and mainly localized in FLS, but insignificant in MLS. Unexpectedly, increased expression of CHOP was observed in PMΦ in arthritis rats. Likewise, cleaved caspase-3 was rarely expressed in MLS. In addition, induction of ER stress by tunicamycin resulted in significantly increased expression of pro-inflammatory molecules such as IL-1β and TNF-α in cultured inflammatory FLS.ConclusionDifferential activation of the ER stress proteins in synovium MLS may contribute to the resistance of synoviocytes to ER stress-induced apoptosis. Furthermore, ER stress is a potential mediator of arthritis inflammation.