Caspase-1对小胶质细胞中NOD2介导的免疫耐受的调节

doi:10.6040/j.issn.1671-7554.0.2014.603

摘要/Abstract

摘要： 目的观察小胶质细胞中是否存在核苷酸结合寡聚化结构域蛋白2(NOD2)介导的免疫耐受现象,并探讨其与Caspase-1的关系.方法分别采用不同浓度的胞壁酸二肽(MDP)或肺炎链球菌刺激小胶质细胞24 h,Western blotting检测各组NOD2和核因子κB(NF-κB)的表达情况,ELISA检测白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的表达情况;用MDP(100 μg/mL)分别预刺激细胞0、3、24 h后再用同浓度MDP刺激24 h,用ELISA检测IL-6和TNF-α的表达量;Caspase-1活性被ATP激活或被其抑制剂抑制后检测IL-6和TNF-α的变化情况.结果与无刺激处理相比,MDP或肺炎链球菌刺激小胶质细胞24 h后,NOD2、NF-κB、IL-6和TNF-α的表达量均明显增加(P<0.05);MDP分别预刺激细胞0、3、24 h后再刺激24 h,发现预刺激3 h和24 h的细胞IL-6和TNF-α的表达量均低于预刺激0 h;通过ATP激活Caspase-1活性可抑制细胞IL-6和TNF-α的表达,抑制Caspase-1活性可促进IL-6和TNF-α的表达.结论长时间MDP刺激可以诱导小胶质细胞的免疫耐受现象,此现象与Caspase-1的活性具有一定关系.

关键词: 核苷酸结合寡聚化结构域蛋白2, 小胶质细胞, 耐受, 三磷酸腺苷, 半胱氨酸蛋白酶-1

Abstract: Objective To investigate whether the nucleotide-binding oligomerization-2(NOD2)-mideated tolerance phenomenon exists in microglia cells and its relationship with Caspase-1 activity. Methods After microglia cells were stimulated with different concentrations of MDP or S.pneumonia for 24 h, the expressions of NOD2 and NF-κB were detected by Western blotting and the expressions of IL-6 and TNF-α were detected by ELISA. After microglia cells were pre-treated with MDP (100 μg/mL) for 0, 3 or 24 h, the expressions of IL-6 and TNF-α were detected by ELISA to verify the NOD2-mediated tolerance in microglia. After Caspase-1 activity was activated or suppressed by ATP or Caspase-1 inhibitor, the expressions of IL-6 and TNF-α were detected by ELISA to observe the relationship between NOD2-mediated tolerance and Caspase-1. Results Compared with no treatment, MDP and S.pneumonia treatment for 24 h significantly increased the levels of NOD2, NF-κB, IL-6 and TNF-α in microglia cells(P<0.05). MDP pretreatment for 3 or 24 h reduced secretion of IL-6 and TNF-α upon subsequent stimulation of MDP for 24 h. Levels of IL-6 and TNF-α were significantly down-regulated by ATP pretreatment, while up-regulated by Caspase-1 inhibitor treatment.Conclusion Prolonged periods of MDP exposure can induce NOD2-mediated tolerance in microglia cells and NOD2-mediated tolerance is associated with Caspase-1 activity.

Key words: Tolerance, ATP, Nucleotide-binding oligomerization-2, Microglia, Caspase-1

中图分类号:

R392.32

袁睿莉, 孙若鹏, 刘心洁. Caspase-1对小胶质细胞中NOD2介导的免疫耐受的调节[J]. 山东大学学报（医学版）, 2015, 53(2): 34-38.

YUAN Ruili, SUN Ruopeng, LIU Xinjie. Caspase-1 activation contributes to Nod2-induced tolerance in microglia cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(2): 34-38.

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