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论著:慢性阻塞性肺病外周血单个核细胞表面TLR2、TLR4的表达与血清TNF α、IL 6、IL 8相关性的研究
Expression of TLR2 and TLR4 on the Surface of Monocytes were Associated with Serum Levels of TNF α, IL 6 and IL 8 in Patients with Chronic Obstructive Pulmonary Disease
龚燕 施小梅 顾洁 刘江霞 金美玲 蔡映云 刘宏炜
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作者单位:复旦大学附属华山医院老年科
中文关键字:慢性阻塞性肺病; Toll样受体; 肿瘤坏死因子 α; 白细胞介素 6; 白细胞介素 8
英文关键字:Chronic obstructive pulmonary disease; Toll like receptors; Tumor necrosis factor alpha; Interleukin 6; Interleukin 8
中文摘要:目的:探讨慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)患者外周血单个核细胞表面Toll样受体(Toll like receptors)TLR2和TLR4的表达情况及其与血清肿瘤坏死因子 α(TNF α)、白细胞介素 6(IL 6)、白细胞介素 8(IL 8)的关系。方法:本研究涉及的3组研究对象分别为:吸烟COPD组(n=68)、吸烟非COPD组(n=42)和不吸烟非COPD组(n=43)。将68例吸烟COPD患者进一步分为急性发作期亚组(n=32)和稳定期亚组(n=36)。采用实时荧光定量PCR法检测外周血单个核细胞表面TLR2、TLR4的表达水平,同时采用酶联免疫吸附试验(ELISA)试剂盒测定血清细胞因子的浓度。结果:吸烟COPD组外周血单个核细胞表面TLR2、TLR4的表达水平及血清TNF α、IL 6、IL 8的浓度均显著高于吸烟非COPD组(TLR2:1.87±2.04比0.47±0.24;TLR4:4.08±3.84比0.41±0.18;TNF α:68.20±56.26比26.20±5.43;IL 6:201.62±174.69比72.99±8.03;IL 8:235.42±158.22比77.50±8.38)。吸烟非COPD组外周血单个核细胞上TLR2、TLR4的表达水平均显著低于不吸烟非COPD组(TLR2:0.47±0.24比2.96±2.71;TLR4:0.41±0.18比2.67±1.74),而吸烟非COPD组血清TNF α、IL 6、IL 8的浓度均显著高于不吸烟非COPD组(TNF α:26.60±5.43比8.93±6.41;IL 6:72.99±8.03比25.61±8.63;IL 8:77.50±8.38比47.10±11.11)。COPD急性发作期单个核细胞表面TLR2、TLR4的表达水平及血清TNF α、IL 6、IL 8的浓度均显著高于COPD稳定期(TLR2:3.56±1.80比0.368±0.222;TLR4:6.97±3.76比1.51±0.943;TNF α:106.17±61.94比90.01±19.66;IL 6:327.18±183.56比105.36±13.45;IL 8:381.74±108.51比34.44±10.45)。吸烟COPD组外周血单个核细胞表面TLR2、TLR4的表达水平与血清TNF α、IL 6、IL 8的浓度成正相关。结论:COPD患者尤其是COPD急性发作期患者外周血单个核细胞表面TLR2、TLR4的表达水平及血清TNF α、IL 6、IL 8的浓度均显著升高;并且COPD患者外周血单个核细胞表面TLR2、TLR4的表达水平与血清TNF α、IL 6、IL 8的浓度成正相关。提示COPD的发生、发展与机体天然免疫密切相关。
英文摘要:Objective:To investigate the expression of Toll like receptor(TLR)2 and TLR4 on the surface of peripheral blood mononuclear cells,as well as the serum levels of tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL 6), interleukin 8 (IL 8) in patients with chronic obstructive pulmonary disease(COPD). Methods: There were three groups in this study: smoking COPD group, smoking healthy group and non smoking healthy group. The COPD group was divided into acute period group and stable period group. Real time fluorescence quantitative PCR assay was used to detect the expression of TLR2 and TLR4, while enzyme linked immunosorbent assay (ELISA) kits were used to detect serum cytokine concentrations. Results: TLR2 and TLR4 expression levels, as well as serum concentrations of TNF α, IL 6 and IL 8 were significantly higher in smoking COPD group than in smoking healthy group (P<0.01). TLR2 and TLR4 expression levels were significantly lower in smoking healthy group than in non smoking healthy group, while TNF α, IL 6, IL 8 concentrations in smoking healthy group were significantly higher compared with non smoking healthy group (P<0.01). The expression levels of TLR2 and TLR4, as well as the serum concentrations of TNF α, IL 6 and IL 8 were significantly higher in acute period COPD group than in stable period COPD group(P<0.01). TLR2 and TLR4 expression levels were positively correlated with serum concentrations of TNF α, IL 6 and IL 8 in COPD patients. Conclusions: TLR2, TLR4 expression levels and serum levels of TNF α, IL 6, IL 8 were significantly increased in COPD patients. It is more significant in acute period COPD. TLR2 and TLR4 expression levels were positively related to serum levels of TNF α, IL 6 and IL 8. COPD’s occurrence and development are correlated with natural immunity.
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