神经生长因子和白血病抑制因子上调哮喘大鼠脾淋巴细胞IL-4、IL-5的表达

Nerve growth factor and leukemia inhibitory factor upregulate the expression of IL-4 and IL-5 in lymphocytes of asthmatic rats

目的:探讨神经生长因子(NGF)、白血病抑制因子(LIF)对哮喘大鼠脾淋巴细胞IL-4、IL-5表达的影响。方法:16只大鼠随机分为对照组(A组)8只,哮喘组(B组)8只,采用卵蛋白和氢氧化铝腹腔内注射致敏,2周后给予1%卵蛋白雾化吸入激发哮喘。(1%卵蛋白/生理盐水)雾化吸入2周后,24h内体外分离培养对照组大鼠和哮喘组大鼠脾淋巴细胞;通过RT-PCR半定量法和ELISA法测定2组大鼠脾淋巴细胞表达Th2细胞因子IL-4、IL-5mRNA转录水平和分泌蛋白的基础水平,观察外源性NGF和LIF体外干预后淋巴细胞IL-4和IL-5表达随干预浓度的变化。结果:(1)哮喘组IL-4、IL-5mRNA表达及蛋白水平明显高于对照组(P<0.05);(2)在外源性不同浓度的NGF、LIF干预下,IL-4、IL-5mRNA和蛋白表达量分别比前一梯度低浓度干预组有显著升高(P<0.05),NGF、LIF上调IL-4、IL-5mRNA和蛋白表达呈浓度依赖性。结论:在哮喘大鼠中,NGF、LIF可能通过上调Th2类细胞因子IL-4、IL-5mRNA表达和蛋白分泌,参与促进和放大Th2类细胞因子免疫失衡效应。

AIM：To investigate the role of nerve growth factor （NGF） and leukemia inhibitory factor （LIF） in the expression of IL-4 and IL-5 in the splenic lymphocytes of asthmatic rats. METHODS：Sixteen Sprague-Dawley rats were randomly divided into two groups：control group （n = 8） and asthma group （n = 8）. The asthmatic model was set up by intraperitoneal injection of 100 mg ovalbumin and 100 mg aluminum hydroxide,and receiving nebulization aspiration of 1% ovalbumin solution 2 weeks later. The splenic lymphocytes from the control rats and asthmatic rats were isolated and cultured with exogenous NGF or LIF at different doses. The mRNA expression of IL-4 and IL-5 in the splenic lymphocytes was respectively detected by reverse transcription-polymerase chain reaction （RT-PCR）. The secretions of IL-4 and IL-5 were respectively detected by ELISA. RESULTS：Compared to control group,the expression of IL-4 and IL -5 （P 0. 05） and the levels of IL-4 and IL-5 （P 0. 05） were both significantly enhanced in asthma group. Exogenous NGF or LIF upregulated the expression and secretion of IL -4 and IL-5 in a dose dependent manner,respectively. CONCLUSION：NGF or LIF may contribute to promote and amplify the immune imbalance of Th2 cells in asthma by upregulating the expression and secretion of IL-4 and IL-5,the Th2 cytokines.