HMGB1、TLR2和TLR4在银屑病中的表达及作用机制研究

Exploring the expression levels of HMGB1, TLR2 and TLR4 and their mechanisms in psoriasis

目的通过检测银屑病患者血清中高迁移率族蛋白1(High mobility group box chromosomal protein 1,HMGB1)及其外周血单核细胞上Toll样受体2(Toll-like receptor 2,TLR2)、Toll样受体4(Toll-like receptor 4,TLR4)的表达,评价其在银屑病的发病机制和病情进展中的作用。方法选取银屑病患者40例,近1个月内未发生感染的健康志愿者20例。采用酶联免疫吸附试验(ELISA)检测血清中HMGB1蛋白的表达,采用流式细胞术分析外周血单核细胞上TLR2、TLR4的表达。采用Pearson相关性分析其与银屑病临床及实验室指标之间的相关性。结果进行期组银屑病患者血清HMGB1表达水平较病情退行期组和对照组明显增高(P<0.05),而退行期组和对照组之间血清HMGB1表达水平无明显差异(P>0.05);进行期组患者血清HMGB1表达水平与ESR、RF和CRP、PASI评分等呈正相关(P<0.05);进行期组银屑病患者外周血单核细胞TLR2和TLR4的表达较退行期组和对照组相比呈上调趋势,而TLR2和TLR4的表达水平在银屑病退行期组和对照组之间无差异;血清中HMGB1的表达水平与单核细胞表面TLR2、TLR4的表达呈正相关。结论血清HMGB1和外周血单核细胞表面TLR2、TLR4均参与了银屑病的病理过程,血清HMGB1和外周血单核细胞表面TLR2和TLR4表达水平增高与银屑病的发病及病情发展有关。HMGB1可能与银屑病患者体内异常的免疫反应有关。血清HMGB1和外周血单核细胞表面TLR2、TLR4的表达在银屑病发病机制中可能具有协同作用。

Objective By detecting the expression of high mobility group box chromosomal protein(HMGB1)in serum,Toll-like receptor 2(TLR2)and TLR4 in monocyte derived macrophage in psoriasis patients,to evaluate its role in the pathogenesis and disease progression in psoriasis.Methods A total of 40 patients with psoriasis were selected,and the control group was 20 healthy volunteers without infection in the last 1 months.Enzyme linked ELISA was used to detect the expression of HMGB1 in serum and the expression of TLR2 and TLR4 in peripheral blood mononuclear cells was analyzed by flow cytometry.Correlation between clinical and laboratory indexes of psoriasis was using Pearson correlation analysis.Results The expression level of HMGB1 in patients with psoriasis in the progressive group was significantly higher than that in the degeneration group and the control group(p<0.05),and there was no difference in the expression of HMGB-1 between the degeneration group and control group(p>0.05);the expression of serum HMGB-1 was positive correlated with ESR,RF,CRP,and PASI scores in the progressive group(p<0.05);the expression of TLR2 and TLR4 in progressive group was up-regulated compared with that in the degenerative group and the control group,while the expression of TLR2 and TLR4 had no difference between the degenerative group and the control group;The expression level of HMGB1 in serum was positively correlated with the expression of TLR2 and TLR4 on monocyte surface.Conclusion The serum HMGB1 level and expression of TLR2 and TLR4 of peripheral blood mononuclear cell surface were involved in the pathogenesis of psoriasis,the upregulated of HMGB-1,TLR2 and TLR4 was related with the occurrence and development of psoriasis.HMGB-1 may be associated with abnormal immune responses in patients with psoriasis.And the serum levle of HMGB-1 and expression of TLR2 and TLR4 on the surface of peripheral blood mononuclear cells may play a synergistic role in the pathogenesis of psoriasis.