摘要
目的探讨在狼疮小鼠脾细胞中是否存在ＩＬ－１２通过Ｌｃｋ／Ｐ３８／ｃ－ｊｕｎ传递信号及其对脾细胞的影响。方法以慢性移植物抗宿主病（ｇｒａｆｔ ｖｅｒｓｕｓ ｈｏｓｔ ｄｉｓｅａｓｅ， ＧＶＨＤ）小鼠为狼疮小鼠模型，分别采用放射自显影、 Ｗｅｓｔｅｒｎ ｂｌｏｔ和Ｎｏｒｔｈｅｒｎ ｂｌｏｔ，检测培养的脾细胞中 Ｌｃｋ的活性、 ｐ３８磷酸化活化及ｃ－ｊｕｎ基因表达的变化。结果狼疮小鼠脾细胞经ＩＬ－１２刺激后，与正常对照组相比较，Ｌｃｋ的活性增高、ｐ３８异常活化，ｃ－ｊｕｎ ｍＲＮＡ的水平增高。加入Ｌｃｋ抑制剂 ＰＰ１组Ｌｃｋ的活性及ｐ３８磷酸化消失，无ｃ－ｊｕｎ基因的表达；加入ｐ３８抑制剂ＳＢ２０３５８０组亦无ｐ３８磷酸化及ｃ－ｊｕｎ基因的表达。结论狼疮小鼠的脾细胞异常，ＩＬ－１２可通过Ｌｃｋ／ｐ３８／ｃ－ｊｕｎ在细胞内传递信号，直接参与免疫损伤。
Aim To investigate whether there is IL-12 signaling pathway through lck/p38/c -jun in splenic cells obtained from lupus mouse and its effect on splenic cells. Methods Mice with graft versus host disease were used as lupus nephritis model. Activity of Lck tyrosine kinase, p38 phosphorylation and mRNA expression of c-jun in splenic cells were determined by autoradiography, Western blot and Northern blot, respectively. Results There were higher levels of Lck activity, p38 phosphorylation and c-jun expression of IL-12-stimulated splenic cells from lupus model when compared with that observed in similarly treated splenic cells from normal control. The Lck activity and p38 phosphorylation were almost inhibited by Lck inhibitor PP1, on the other hand, p38 specific inhibitor SB203580 decreased phosphorylation of p38. In addition, expression of c-Jun was also inhibited by PP1 or SB203580 although splenic cells were stimulated with IL-12. Conclusion Aberrant murine splenic call, IL-12-me- diated intracelluar signaling pathway through lck/p38/c-Jun were involved in immunologic damage.
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2001年第1期32-34,共3页
Chinese Journal of Cellular and Molecular Immunology
基金
卫生部基金资助!No.94-1-105
