慢性鼻窦炎黏膜组织中转录因子GATA-3与局部细胞因子表达的相关性

Relationship between transcription factor GATA-3 and cytokines expression in chronic sinusitis

目的探讨慢性鼻窦炎筛窦勃膜组织中GAT:A-3与局部细胞因子(IL-5 , IL-6 , IL-8 )表达的关系。方法采用酶联免疫吸附测定法(enzyme-linked immunusorbent assay,ELISA)检测45例慢性鼻窦炎筛窦戮膜〔根据是否伴变应性鼻炎(allergic rhinitis , AR ),分成伴有AR(AR组,28例)和不伴有AR(NAR组,17例)两组」与11例因脑脊液鼻漏、视神经管减压而行鼻内镜手术患者的筛窦私膜(对照组)组织中IL-5 , IL-6和IL-8的含量。半定量反转录一聚合酶链反应(reverse transcription-polymerase chain reaction, RT-PCR)和免疫组织化学法检测GATA-3在筛窦勃膜中的表达,分析GATA-3表达与局部细胞因子含量间的相关性。结果3组患者筛窦赫膜组织中AR组与NAR组的IL-S,IL}b和IL-8水平均高于对照组,差异具有统计学意义(P值均<0. OS ) ; AR组的3种细胞因子水平均高于NAR组,差异具有统计学意义(P值均<0. 01)。半定量RT-PCR所得的相对密度显示AR组和NAR组的GATA-3 mRNA水平高于对照组(P值均<0. 01),同时AR组的GATA-3 mRNA水平又高于NAR组,差异具有统计学意义(Y<0.01)。免疫组化结果显示,GA'Z'A一主要在细胞质内表达,且G.4TA一阳性细胞主要为砧膜下的炎症浸润细胞。平均胞质染色阳性率AR组为(27. 92士16. 75 ) % , NAR组为(10. 22士0.05)%,对照组为(1. 30士1. 78 ) % o AR组和NAR组的慢性鼻窦炎患者GATA-3的胞质阳性率高于对照组,差异具有统计学意义(P值均<O.OI),AR组又高于NAR组,差异具有统计学意义(P < 0. O1) o Pearson相关性分析结果显示,GATA-3的胞质染色阳性率与鼻窦炎患者局部IL-5水平之间存在相关性(r=0.712,P<0.01)a GATA-3的胞质染色阳性率与IL-6,IL-8水平缺乏相关性(r分别为0. 200与0. 089 , P值均>0.05)结论慢性鼻窦炎中GATA-3激活是诱导局部IL-5表达的可能机制之一,变应性鼻炎的存在可以进一步提高GATA一的活性,进而增加局部IL-5的表达。慢性鼻窦炎的发生发展与变态反应有一定的关系,GATA-3在慢性鼻窦炎的发病机理中可能是关键因素之一。ILK和IL-8的局部表达不依赖于GATA-3途径。

Objective To explore the correlation between the expression of GATA-3 and the level of local cytokines （IL-5, IL-6 and IL-8）. Methods The levels of IL-5, IL-6 and IL-8 in ethmoid sinus mucosa were titrated in 45 patients with chronic rhinosinusitis and 11 normal subjects by ELISA. Patients were divided into AR group （with allergic rhinitis） and NAR group （without allergic rhinitis ）. Semiquantitative RT-PCR and immunohistochemical staining were used to examine the GATA-3 expression nasal mucosa. The correlation between the expression of GATA-3 and the levels of cytokines was evaluated. Results IL-5, IL-6 and IL-8 levels in both AR and NAR groups were significantly elevated compared with normal group （ all P 〈0. 01 for AR group; P 〈0. 05, 0. 05, 0. 01 for NAR group, respectively）, and they were much higher in AR group in comparison with NAR group （ P 〈 0.01, 0. 05, 0.01, respectively ）. Semi-quantitative RT-PCR showed that AR and NAR groups had markedly greater level of GATA-3 mRNA than that in control group （ P 〈 0. 01, respectively）, and the level of GATA-3 mRNA in AR group was further higher than that in NAR group （P 〈 0. 01 ）. Immunohistochemical staining illustrated that GATA-3 was primarily presented in cytoplasma and the GATA-3 positive cells were mainly infiltrating inflammatory cells in submucosa. The mean GATA-3 positive-staining rate was （ 27.90 ± 16. 75 ） % and （ 10. 22 ± 0. 05）% in AR and NAR group, which were markedly higher than （ 1.30 ± 1.78）% in control group （P 〈 0. 01 ,respectively）. Pearson correlation analysis demonstrated that GATA-3 positive-staining rate was closely correlated with IL-5 level, but not IL-6 and IL-8. The correlation coefficient was 0. 712 for GATA-3 and IL-5 （P〈0.01）, 0.200 for GATA-3 and IL-6 （P〉0.05）, 0.089 for GATA-3 and IL-8 （P〉0.05）. Conclusions Activation of GATA-3 might be one of the mechanisms for induction of IL-5 expression in chronic rhinosinusitis . Concomitance of allergic rhinitis with chronic rhinosinusitis further increased expression of GATA-3, and subsequently enhanced IL-5 expression. Chronic sinusitis may be related to allergy, and GATA-3 may play a key role in the pathogenesis of chronic sinusitis.