The correlation between the expression of differential drug-resistant proteins and inflammatory cyto-kines in collagen-induced arthritis model
10.3760/cma.j.issn.1007-7480.2019.03.003
- VernacularTitle:ATP结合盒转运蛋白在胶原诱导性关节炎 模型鼠的差异表达及其与血清炎性细胞因子的相关性研究
- Author:
Jie LIANG
1
;
Xiangcong ZHAO
;
Hongqing NIU
;
Yanfei MU
;
Zhaohua LI
;
Xiaofeng LI
;
Caihong WANG
Author Information
1. 山西医科大学第二医院风湿免疫科
- Keywords:
Arthritis,rheumatoid;
P-glycoprotein;
ATP-binding cassette transporters;
Cytokines
- From:
Chinese Journal of Rheumatology
2019;23(3):153-159,后插1
- CountryChina
- Language:Chinese
-
Abstract:
Objective We investigated the correlation between inflammatory cytokines and drugresi-stant proteins. Methods Fourteen DBA1 mice were successfully induced by collagen and Freund's adjuvant. According to the scores of synovial pathology, the collagen-induced arthritis (CIA) group was divided into mild, moderate-severe groups, another four mice were selected as controls. The mRNA expressions of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein 1 (MRP1) in splenic lymphocyte cells were measured by reverse transcription-polymerase chain reaction (RT-PCR). The concentrations of inter-leukin (IL)-1β, IL-2, IL-6, IL-10, umor necrosis factor (TNF)-α, IL-17 in serum were detected by Cytometric Bead Array (CBA). The correlation between different inflammatory cytokines and these proteins were analyzed, then one of the proteins which were most related with cytokines by immunohisto-chemical (IHC) in the synovium was studied. Data were analyzed by the Mann-Whitney U test, Kruskal-Wallis H test and spearman analysis. Results ①Compared with normal controls, the levels of IL-6 and TNF-α in the serum of mild CIA group, moderate-severe CIA group were significantly increased {IL-6 controls: [7.75 (5.14, 9.17) pg/ml];mild CIA: [25.31 (15.15, 29.27) pg/ml]; modeate-severe CIA: [45.03 (38.87, 64.02) pg/ml]. TNF-α: controls: [22.81 (20.84, 28.17) pg/ml]; mild CIA: [45.00(32.76, 58.51) pg/ml]; modeate-severe CIA: [45.00(39.78, 8.95) pg/ml]}(Z=14.383, P<0.05; Z=8.375, P<0.05). Compared with the mild CIA group, the level of IL-6 in serum was significantly increased in the moderate-to-severe CIA group (P<0.05), but there was no signigicant difference in the TNF-α level (P>0.05). ② In the spleen lymphocytes, there was no significant difference in the mRNA expression level of P-gp and BCRP among the groups, but the mRNA expression level of MRP1 was significantly increased (Z=12.634, P<0.05). Compared with the mild CIA group, the MRP1 mRNA in the moderate-severe CIA group was higher, the difference was significant (Z=12.634, P<0.05). There was a correlation between mRNA expression of MRP1 and P-gp (r=0.635, P=0.015). ③ The mRNA expression of MRP1 was positively correlated with IL-6 level (r=0.711, P=0.004). ④ The expression of MRP1 in normal group, low-level IL-6 group and high- IL-6 level group were as follows: [1.08 (0.65, 1.30)], [1.32 (1.08, 1.49)], [2.07 (1.77, 2.22)] respectively.⑤Compared with the controls, the cytoplasm/membrane of the knee and ankle joint synovial tissue in the CIA group was yellowish-brown, which indicated that MRP1 expression was positive. Conclusion In the CIA arthritis model, synovial tissue lesion is not only related to inflammatory cytokines, but also related to MRP1 expression in the ATP-binding cassette (ABC) transport protein family, and it is proved that IL-6 is highly correlated to MRP1.
