慢性鼻-鼻窦炎炎性黏膜中核转录因子-κB活性与局部三种细胞因子表达的关系

目的探讨慢性鼻-鼻窦炎炎性黏膜中核转录因子-κB（nuclear factor-kappa B，NF—κB）活性与局部3种细胞因子表达的关系。方法采用酶联免疫吸附方法检测52例慢性鼻-鼻窦炎[根据是否伴变应性鼻炎（allergic rhinitis，AR），分为AR组与NAR组]与12例正常筛窦黏膜组织中IL-5、IL-6及IL-8含量，半定量RT—PCR和免疫组织化学法检测NF—κB亚单位P50、P65在鼻黏膜的表达及活性，分析NF-κB各亚单位的活性与IL-5、IL-6及IL-8含量间的相关性。结果AR组与NAR组筛窦黏膜中IL-5、IL-6、IL-8水平均显著高于正常组（AR组P值均〈0．01；NAR组P值分别〈0．05、0．05、0．01）；AR组的3种细胞因子水平均明显高于NAR组（P值分别〈0．01、0．05、0．01）。半定量RT—PCR显示，AR组与NAR组P50、P65的mRNA表达水平均显著高于正常组（AR组P值均〈0．01；NAR组P值均〈0．01）；AR组明显高于NAR组（P值均〈0．05）。免疫组化显示AR及NAR两组P50、P65核染阳性率均显著高于正常组（P值均〈0．01）；AR组较NAR组更高（P值均〈0．01）。Pearson相关性分析显示，P50、P65核染阳性率与局部IL-6、IL-8水平存在显著相关性，其中P50与IL-6、IL-8的相关系数分别为0．49与0．54（P值均〈0．01）；P65与两者的相关系数分别为0．61与0．66（P值〈0．01）。P50、P65核染阳性率与IL-5间无明显相关性。结论慢性鼻-鼻窦炎炎性黏膜中NF—κB的P50、P65两个亚单位的核转位及活化是诱导局部IL-6、IL-8表达的可能机制之一，AR的并存可进一步提高NF-κB活性，进而增加局部IL-6、IL-8的表达。IL-5的局部表达不依赖于NF-κB途径。

Correlative study of nuclear factor-kappa B activity and cytokine expression in chronic sinusitis

OBJECTIVE: To investigate the correlation between nuclear factor-kappa B (NF-kappaB) activity and cytokine expression in nasal mucosa of chronic sinusitis. METHODS: IL-5, IL-6 and IL-8 levels in nasal mucosa were assayed by the method of ELISA in 52 cases of chronic sinusitis [concomitant with allergic rhinitis (AR group), without allergic rhinitis (NAR group)] and 12 normal subjects. Semi-quantitative RT-PCR and immunohistochemical staining were used to examine P50 and P65 subunits of NF-KB expressions and activation in nasal mucosa. The correlation between activities of NF-KB P50 and P65 subunits and cytokine expression was evaluated. RESULTS: IL-5, IL-6 and IL-8 levels in both AR and NAR groups were significantly increased (all P < 0.01 for AR group; P < 0.05, 0.05, 0.01, respectively, for NAR group, as compared with normal group), and the levels were much higher in AR group than that in NAR group (P < 0.01, 0.05, 0.01, respectively). The levels of P50 and P65 mRNA in both AR and NAR groups were enhanced (all P < 0.01 for AR group; all P < 0.01 for NAR group, as compared with normal group), and AR group had markedly greater P50 and P65 mRNA levels in comparison with NAR group (both P < 0.05). Immunohistochemical study revealed that nucleus-present rates of P50 and P65 in both AR and NAR groups were significantly higher than those of control group (all P < 0.01), and they were much greater in AR group as compared with NAR group (all P < 0.01). Pearson correlation analysis demonstrated that P50 and P65 nucleus-present rates were closely correlated with IL-6 and IL-8 levels, but not IL-5. The correlation coefficient was 0. 49 for P50 and IL-6, 0. 54 for P50 and IL-8, 0. 61 for P65 and IL-6, and 0.66 for P65 and IL-8 (all P < 0.01). CONCLUSIONS: Activation of P50 and P65 subunits of NF-kappaB might be one of the mechanisms for induction of IL-6 and IL-8 expression in chronic sinusitis. Concomitance of allergic rhinitis with chronic sinusitis further increased activities of NF-kappaB subunits, and further elevated IL-6 and IL-8 expression. IL-5 expression was independent of NF-kappaB pathway in chronic sinusitis.