鼻息肉中NF-κB的活化对IL-8转录的影响及意义

Effects of NF-кB activation on the transcription of IL-8 in human nasal polyps

目的通过检测鼻息肉组织中核因子кB(NF-кB)的活化及白介素-8(IL-8)的转录水平,探讨鼻息肉组织中NF-кB的活化对IL-8转录的影响及临床意义。方法分别应用凝胶电泳迁移实验法、蛋白免疫印迹法、免疫组织化学法及逆转录聚合酶链反应法检测47例鼻息肉患者(鼻息肉组)的息肉组织中NF-κB的活性及其p65亚基蛋白水平、IL-8的组织定位及转录水平;以22例鼻中隔手术患者中鼻甲黏膜组织作为阴性对照(对照组);对NF-кB的活性及其p65亚基蛋白水平与IL-8的转录水平进行Pearson’s相关性分析。结果 EMSA测得鼻息肉组患者息肉组织中NF-κB的活性(216.51±17.33)较对照组(63.57±5.26)显著增高(P<0.01);Western Blot测得鼻息肉组NF-κB亚基p65蛋白的水平(153.72±9.15)较对照组(73.92±6.74)显著增高(P<0.05);半定量RT-PCR测得IL-8mRNA的转录水平(0.95±0.08)也显著高于对照组(0.23±0.03)(P<0.05);Pearson’s相关性分析结果提示:鼻息肉组患者息肉组织中NF-κB的活性及其p65亚基蛋白水平与IL-8的转录水平呈显著正相关性(r值分别为0.78&0.53,均P<0.01)。结论 IL-8是鼻息肉组织中NF-кB激活后所分泌的重要的炎性细胞因子,NF-кB和IL-8引起的局部微环境的改变可能是鼻息肉发病的重要因素。

Objective To investigate the effects of NF-кB activation on transcription of IL-8 in the tissues of nasal polyps. Methods The specimens from 47 nasal polyps （nasal polyp group） and 22 nasal septurn mucous membranes （control group） were studied by electro-phoretic mobility shift assay （EMSA） for the activation of NF-кB, by Western Blot for the protein level of NF-кB p65 subunit, by reverse-transcription polymerase chain reaction （RT-PCR）for the transcriptions of IL-8 mRNA and by immunohistochemistry for the location of IL-8. The correlations among the activation of NF-кB,the protein level of NF-кB p65 subunit and the transcriptions of 1L-8 mRNA were evaluated by Pearson correlation analysis. Results The activation of NF-кB and the protein level of NF-кB p65 subunit were significantly increased in the tissues of nasal polyps compared those of the coutrols（P〈0.01＆ P〈0.05）. The transcription of IL-8 mRNA was significantly increased in nasal polyps than that in the control group （P〈0.05）. The Pearson correlation analysis demonstrated that there were positive relationship between the activations of NF-кB and the tran- scription of IL-8 （r=0.78） and between the protein levels of NF-кB p65 subunit and the transcriptions of IL-8 （r=0.53, all P〈0.01）. Conclusion These results suggest that IL-8 regulated by NF-кB may be a key cytokine in nasal polyps. The changes in the microenvironment caused by NF-кB and IL-8 may play an important role in the mechanisms for the pathogenesis of nasal polyps.