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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。
OBJECTIVE: To investigate the presence or absence of transcripts that support the UPR hypothesis and the involvement of those cells in unfolded protein responses by studying the gene profile of peripheral blood mononuclear cells (PBMC) synovial fluid mononuclear cells (SFMCs) in patients with ankylosing spondylitis (AS) (UPR), UPR in patients with AS and its role in the pathogenesis of arthritis and its significance. Methods: Gene expression profiles of PBMCSFMC from patients with AS were obtained by cDNA microarray scan with 1176 gene. The results showed that genes of C2, C3, C8, LMP2, LMP7 and BiP (UPR) that were differentially expressed in healthy volunteers and RA patients Markers) and then RTPCR verification. Results: BiP expression was significantly higher in patients with AS than in those with RA (SFTP) (mean and standard deviation of RTPCR were 86.4 ± 111.3 and 18.5 ± 13.0, P = 0.044 for both) C2 were 91.6 ± 36.7 and 18.5 ± 3.6, respectively (P <0.037 for both), and the increased levels of BiP and UPR-associated proteasome C2 in the SFMC of patients with AS were closely related (r = 0.9). In addition, the study also found that AS patients SFMC over-expression of BiP cells are mononuclear macrophages. Conclusion: Endoplasmic reticulum UPR does occur in macrophages in SFMC of AS patients. The results showed that UPR response plays an important role in the early stage and continuation of joint inflammation in AS patients.