Dong W, Zhang Y, Yan M, Liu H, Chen Z, Zhu P
Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Scand J Rheumatol. 2008 Nov-Dec;37(6):427-34. doi: 10.1080/03009740802213310.
To investigate the expression of the 78-kDa glucose-regulated protein (GRP78), a marker of activation of the unfolded protein response (UPR), in macrophages of ankylosing spondylitis (AS) synovium and synovial fluid and to explore the relationship between the expression of GRP78 and synovial fluid levels of the proinflammatory cytokines, as well as the inflammatory activity of AS.
Immunohistochemical staining and Western blotting were performed to detect the expression of GRP78 in macrophages in the involved peripheral joints of 16 patients with active AS, and in 15 patients with osteoarthritis (OA) as controls. Synovial fluid levels of tumour necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) of AS peripheral joints were measured using an enzyme-linked immunosorbent assay (ELISA). The inflammatory activity of AS was measured by the sera levels of IL-6 and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).
Expression of GRP78 in macrophages was increased significantly in the affected peripheral joints of AS compared with OA patients. Positive correlations were found between the expression of GRP78 in macrophages in AS-affected peripheral joints and the synovial fluid levels of TNFalpha and IL-6, as well as the sera levels of IL-6 and the BASDAI.
Activation of the UPR occurs in macrophages in both the synovium and synovial fluids of AS-involved peripheral joints, and there may be a link between activation of the UPR of macrophages and local production of the proinflammatory cytokines, as well as the inflammatory activity of AS.
研究78 kDa葡萄糖调节蛋白（GRP78）（未折叠蛋白反应（UPR）激活的标志物）在强直性脊柱炎（AS）滑膜和滑液巨噬细胞中的表达，并探讨GRP78表达与促炎细胞因子滑液水平以及AS炎症活动之间的关系。
对16例活动期AS患者受累外周关节的巨噬细胞以及15例骨关节炎（OA）患者作为对照进行免疫组织化学染色和蛋白质印迹，以检测GRP78的表达。采用酶联免疫吸附测定（ELISA）法检测AS外周关节滑液中肿瘤坏死因子-α（TNFα）和白细胞介素-6（IL-6）的水平。通过血清IL-6水平和巴斯强直性脊柱炎疾病活动指数（BASDAI）来衡量AS的炎症活动。
与OA患者相比，AS患者受累外周关节巨噬细胞中GRP78的表达显著增加。AS受累外周关节巨噬细胞中GRP78的表达与TNFα和IL-6的滑液水平、IL-6的血清水平以及BASDAI之间存在正相关。
在AS累及外周关节的滑膜和滑液巨噬细胞中均发生了UPR激活，巨噬细胞UPR激活与促炎细胞因子的局部产生以及AS的炎症活动之间可能存在联系。
