Increased response to activated Toll-like receptor 4 in peripheral blood mononuclear cells from patients with rheumatoid arthritis modulate the differentiation of Thl7 cells
10.3760/cma.j.issn.1007-7480.2011.12.005
- VernacularTitle:活化的类风湿关节炎患者外周血单个核细胞Toll样受体4诱导Th17细胞分化
- Author:
Lei QIAN
;
Lijun LV
;
Ming XU
;
Xiaoying WANG
- Publication Type:Journal Article
- Keywords:
Arthritis,rheumatoid;
T-lymphocytes,helper-inducer;
Peripheral blood mononuclear cells;
Toll-like receptor 4
- From:
Chinese Journal of Rheumatology
2011;15(12):816-820
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of Toll-like receptor 4 (TLR4) on the peripheral blood mononuclear cells(PBMCs) in the development of rheumatoid arthritis (RA) by inducing the differentiation of Th17 cells.Methods Forty two subjects were recruited to the study,including 22 patients with RA and 20 healthy controls (HC).The percentage of circulating Th17 cells were analyzed using flow cytometry.PBMCs were stimulated with LPS for two days.TLR4 mRNA of the PBMCs and the concentration of IL-6 and TNF-α in the supernatants were analyzed with the real-time qPCR and ELISA respectively.Supematants was then used for CD4+ cord blood mononuclear cells (CBMCs) culture,and IL-17 in the supernatants and the expression of IL-17 mRNA in cells were detected by ELISA and real-time qPCR respectively.The statistical analysis was carried out with t-test.Results The TLR4 mRNA expression in the PBMCs and the percentage of circulating Th17 ceils of RA patients were significantly higher than that of the HC group (P＜0.01).Stimulated by LPS,the expression of TLR4 mRNA increased 3.5 times in the RA group but decreased 0.11 times in the HC group.LPS also increased cytokines production in both groups,while PBMCs from RA patients produced more IL-6 and TNF-α than the cells from healthy subjects (P＜0.01).Compared to the HC group,the IL-17 mRNA expression and IL-17 secretion of CD4+ CBMCs induced by the supematants of RA patients' PBMCs stimulated with LPS was significantly higher(P＜0.01 ); but there was no significant difference between the RA group and the HC group without LPS stimulation (P＞0.05).Conclusion The expression of TLR4 on PBMCs from patients with RA and its response to LPS stimulation are increased,and it has demonstrated high capability in inducing the differentiation of Th 17 cells.
