未折叠蛋白应答在强直性脊柱炎发病机制中的意义探讨

目的:通过研究强直性脊柱炎(AS)病人的外周血单个核细胞(PBMC)关节液单个核细胞(SFMC)的基因谱,了解有无支持UPR假说的转录物以及那些细胞参与未折叠蛋白应答(UPR),UPR在AS病人的变化及其在关节炎发病机制中的作用和意义。方法:AS病人的PBMCSFMC基因表达谱通过含1176基因的cDNA微阵列扫描得到,结果中比较AS与健康自愿者和RA病人有差异表达的基因C2、C3、C8、LMP2、LMP7和BiP(UPR的标志物)再以RTPCR验证。结果:AS患者的SFMC中的BiP表达显著高于RA患者SFMC组(RTPCR的均数和标准差为86.4±111.3和18.5±13.0,两者比较,P=0.044),AS和RA患者SFMC组的C2分别为91.6±36.7和18.5±3.6(两者比较,P<0.037),而且AS患者的SFMC中BiP和UPR相关的蛋白酶体C2的增高水平密切相关(相关系数r=0.9)。另外,研究还发现,AS患者SFMC过度表达BiP的细胞是单核巨噬细胞。结论:内质网UPR确实发生在AS患者SFMC中的巨噬细胞。结果显示UPR应答在AS病人关节炎症的初期和延续中起重要的作用。

Unfold protein response in the pathogenesis of ankylosing spondylitis

Objective:To determine the expression of genes of PBMC/SFMC in AS patients which related with the role of unfolded protein response(UPR) of endoplasmic reticulum and discuss their roles and meanings in the pathogenesis of AS.Methods:Gene expression profiles of peripheral blood mononuclear cells(PBMC) and synovial fluid mononuclear cells(SFMC) in AS,healthy volunteers and RA patients were determined by cDNA microarray with 1176 target gene filter.Differently expressed C2,C3,C8,LMP-2,LMP-7 and BiP were confirmed by semi-quantitative RT-PCR.Results:The proteasome C2 in 1176 gene expression profiles of SFMC in AS patients was significantly different from those of RA.Higher expression of proteasome C2 and BiP in SFMC of AS patients were found with statistical significance(P=0.037 and 0.044) compared to those of RA patients by semi-quantitative RT-PCR.The correlation coefficient of BiP and proteasome C2 was 0.9.The higher expression of BiP in SFMC was mainly found in macrophage.Conclusion:There are UPR in macrophage of SFMC in AS patients.UPR may play a potential key role in the initiation and continuation of joint inflammation in AS patients.