活動性全身性紅斑狼瘡病患周邊血液單核球類鐸蛋白受體的表現和功能分析

Abstract

紅斑性狼瘡 (Systemic lupus erythematosus, SLE) 患者被發現得到細菌性感染的機率比正常人高。過去研究已知類鐸蛋白受體(toll-like receptors, TLRs)在微生物感染的控制上扮演重要的角色，本研究的主題在比較未治療的SLE病患和正常受試者類鐸蛋白受體的表達量及功能的不同，以探討在免疫力缺陷狀態的SLE病患，類鐸蛋白受體的貢獻為何。類鐸蛋白受體的表達量以流式細胞儀分析後，結果發現CD14巨嗜細胞上TLR2和TLR4的表達量，SLE病患比正常受試者低，TLR9的表達量，SLE病患比正常受試者高。單核球分別以ligands for TLR-2，TLR-4，TLR-9刺激活化，其上清液和血漿利用酵素免疫分析法 (Enzyme-linked immunosorbent assay, ELISA)分析細胞激素的表達量，結果發現經由LPS、CpG ODN、sBLP刺激PBMC生成IL-1和TNF-alpha，在SLE病患均比正常受試者低。由研究結果得知，SLE病患鐸蛋白受體在monocytes的調控和正常受試者不同，以及經由這三種鐸蛋白受體路徑活化的免疫系統在SLE病患製造細胞激素也和正常受試者不同，這可能和SLE病患免疫力缺陷的狀態相關。

SLE patients have been shown to have the higher susceptibility to infectious diseases. Since Toll-like receptors (TLRs) play an important role in controlling microorganism infection, this study has been aimed to compare the expression and function of some TLRs in SLE with those in normal individuals to test the possible contribution of TLRs to the immuno-compromised status in SLE patients. The protein expression levels of TLR-2 TLR-4 and TLR-9 were assayed by flow cytometric analysis, and it was found that, compared with normal individuals, SLE patients expressed the lower levels of TLR-2 and TLR-4, but the higher TLR-9 levels on CD14+ monocytes. The cytokine expression in sera of SLE patients and normal individuals and in the supernatant of lupus and normal PBMCs stimulated with ligands for TLR-2, TLR-4 and TLR-9 were determined by ELISA to be compared the cytokine expression in SLE with those in normal individuals. It was found that PBMCs stimulation by LPS, CpG ODN, and sBLP resulted in attenuated IL-10 and TNF-alpha protein production in SLE patients. These results suggested that the dysregulation of TLRs expression on monocytes and abnormal cytokine production from PBMCs after TLR ligation may be involved in the development of immuno-compromised status in SLE patients.