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[Th1/Th2细胞因子免疫失衡对哮喘中神经生长因子表达的影响]

[Effect of Th1/Th2 cytokine immune imbalance on the expression of nerve growth factors in asthma].

作者信息

Ouyang Ruo-Yun, Hu Cheng-Ping, Chen Ping, Zhu Jin-Qi, Huang Xin-Gang

机构信息

Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007 Feb;32(1):119-23.

Abstract

OBJECTIVE

To explore the effect of Th1/Th2 cytokines on the expression of nerve growth factor(NGF)in splenic lymphocytes in asthmatic model.

METHODS

Four SD rats were sensitized and challenged with ovalbumin to establish an asthmatic model, and the rat splenic lymphocytes were isolated and cultured with ConA. The expressions of NGF mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and were observed after the lymphocytes were exogenously added with interferon-gamma(IFN-gamma) or interleukin-4 (IL-4).

RESULTS

The lymphocytes of the asthmatic model stimulated by ConA in vitro expressed NGF mRNA in a time-dependent manner. After the lymphocytes had been cultured with IL-4 for 12 h, 24 h, 36 h, and 48 h, 50 microg/L IL-4 upregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly higher than the basal values at the same time(all Ps<0.01). After 0, 10, 50, and 100 microg/L IL-4 had been added for 24 h, IL-4 upregulated the expressions of NGF mRNA in a dose-dependent manner and the NGF mRNA expressions were all significantly higher than the values of the lower dose IL-4(all Ps<0.05). After the lymphocytes had been cultured with 10 mug/L IFN-gamma for 0 h, 12 h, 24 h, 36 h, and 48 h, IFN-gamma downregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly lower than the basal values at the same time(all Ps<0.01). After 0, 1, 10, and 50 microg/L IFN-gamma have been added for 24 h, IFN-gamma downregulated the expressions of NGF mRNA in a dose-dependent manner and all the NGF mRNA expressions were significantly lower than the values of the lower IFN-gamma dose(all Ps<0.05).

CONCLUSION

In the splenic lymphocytes of asthmatic rats, IL-4, one of the Th2 cytokines, can upregulate the expressions of NGF; IFN-gamma, one of the Th1 cytokines, can downregulate the expressions of NGF both in a time-dependent manner and in a dose-dependent manner. Th1/Th2 cytokine immune imbalance may indirectly induce the airway neurogenic inflammation by regulating the NGF mRNA expression.

摘要

目的

探讨Th1/Th2细胞因子对哮喘模型大鼠脾淋巴细胞神经生长因子(NGF)表达的影响。

方法

4只SD大鼠用卵清蛋白致敏并激发以建立哮喘模型,分离大鼠脾淋巴细胞并用刀豆蛋白A(ConA)进行培养。采用逆转录-聚合酶链反应(RT-PCR)检测NGF mRNA的表达,在外源性添加干扰素-γ(IFN-γ)或白细胞介素-4(IL-4)后观察其表达情况。

结果

体外经ConA刺激的哮喘模型淋巴细胞呈时间依赖性表达NGF mRNA。淋巴细胞用IL-4培养12 h、24 h、36 h和48 h后,50 μg/L IL-4呈时间依赖性上调NGF mRNA的表达,且各时间点NGF mRNA表达均显著高于同一时间的基础值(均P<0.01)。添加0、10、50和100 μg/L IL-4 24 h后,IL-4呈剂量依赖性上调NGF mRNA的表达,且各剂量组NGF mRNA表达均显著高于低剂量IL-4组(均P<0.05)。淋巴细胞用10 μg/L IFN-γ培养0 h、12 h、24 h、36 h和48 h后,IFN-γ呈时间依赖性下调NGF mRNA的表达,且各时间点NGF mRNA表达均显著低于同一时间的基础值(均P<0.01)。添加0、1、10和50 μg/L IFN-γ 24 h后,IFN-γ呈剂量依赖性下调NGF mRNA的表达,且各剂量组NGF mRNA表达均显著低于低剂量IFN-γ组(均P<0.05)。

结论

在哮喘大鼠脾淋巴细胞中,Th2细胞因子之一IL-4可上调NGF的表达;Th1细胞因子之一IFN-γ可呈时间依赖性和剂量依赖性下调NGF的表达。Th1/Th2细胞因子免疫失衡可能通过调节NGF mRNA表达间接诱导气道神经源性炎症。

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