实验性自身免疫性脑脊髓膜炎小鼠中IL-27对CCL5表达的影响

Effect of IL-27 on CCL5 expression in experimental autoimmune encephalomyelitis mice

目的探讨白介素-27(interleukin-27,IL-27)对中枢神经系统(central nervous system,CNS)炎性趋化因子(chemokine RANTES,CCL5)的调节作用,以及在小鼠实验性自身免疫性脑脊髓膜炎(experimental autoimmune encephalomyelitis,EAE)中的治疗效果。方法 40只雌性C57BL/6小鼠建模后,分别于第0、7、14、21天用Western blot检测CNS中IL-27和CCL5的变化。另将50只小鼠随机分为正常组、EAE组、EAE+IL-27组、EAE+SC144(IL-27受体抑制剂)组和EAE+PBS组,定期观察动物行为变化,并在建模后21 d检测CCL5的表达。结果建模后,IL-27在CNS中的表达随时间逐渐升高,而CCL5的表达随时间先升高后下降。经IL-27干预后,小鼠神经功能缺损较对照减轻(P<0.05),而SC144组小鼠神经功能缺损较其他组加重(P<0.05)。在21 d,CCL5在IL-27干预组的表达较EAE模型组明显降低(P<0.05),而在SC144组较EAE模型组显著增高(P<0.05)。结论在EAE模型中,IL-27抑制CCL5的表达,从而发挥抗炎作用减轻小鼠神经功能缺损。

Objective To determine regulating effect of interleukin-27 （IL-27） on the expression of central nervous system （CNS） chemokine RANTES （CCL5）, and investigate its therapeutic effect on experimental autoimmune encephalomyelitis （EAE） in mice. Methods EAE models were established in 40 female C57BL/6 mice by inoculating homogenate containing myelin oligodendrocyte glycoprotein （MOG31-55） and complete Freund’s adjuvant （CFA）, and then the rabbits were killed in 0, 7, 14 and 21 d later for the expression of IL-27 and CCL5 in the CNS by Western blotting. Another 50 female C57BL/6 mice were randomly divided into normal control group, EAE group, EAE＋IL-27 group, EAE＋SC144 （IL-12 receptor inhibitor） group and EAE＋PBS group. The behavior changes were observed. The expression of CCL5 at protein and mRNA levels was detected in the CNS by Western blotting and real-time PCR in 21 d after EAE model establishment. Results After EAE model was established, the expression of IL-27 in the CNS was increased with time elapse, while the expression of CCL5 was reduced with time. IL-27 intervention resulted in milder injury in neural function （P〈0.05）, while SC144 treatment enhanced the injury （P〈0.05）. In 21 d after EAE model establishment, the mRNA and protein expression of CCL5 was significantly decreased in the IL-27 intervention group than the EAE model group （P〈0.05）, while the expression was increased significantly in SC144 group （P〈0.05）. Conclusion In EAE mice, IL-27 suppresses the expression of CCL5 at protein and mRNA levels, and thus exerts an anti-inflammatory effect to reduce the nerve function, which might provide a new drug target for CNS autoimmune inflammatory disease.