| 摘要: |
| 目的:探讨高迁移率族蛋白1（HMGB1）能否激活巨噬细胞表达IL-18及其受体。方法:HMGB1与小鼠腹腔巨噬细胞共孵育后，采用实时RT-PCR、ELISA和流式细胞术分别检测IL-18的基因表达和蛋白含量以及IL-18受体(IL-18R)表达水平。Toll样受体（Toll-like receptor，TLR）2激动剂Pam3Cys(1 μg/ml)和TLR4激动剂脂多糖（LPS，100 ng/ml)设为平行对照。结果:100 ng/ml HMGB1刺激巨噬细胞2 h，IL-18 mRNA的表达明显增加；HMGB1刺激24 h后IL-18蛋白的产生明显增加，并且轻度上调细胞表面IL-18R的表达。TLR2激动剂Pam3Cys和TLR4激动剂LPS也能促进IL-18的基因表达和蛋白产生以及上调IL-18R的表达。结论:HMGB1可以直接激活巨噬细胞表达IL-18及其受体，提示HMGB1在炎症反应中可能通过IL-18加强致炎作用。 |
| 关键词: 类风湿关节炎 高迁移率族蛋白1 巨噬细胞 白细胞介素18 |
| DOI：10.3724/SP.J.1008.2009.01353 |
| 投稿时间：2009-04-17修订日期：2009-09-07 |
| 基金项目:国家自然科学基金(30872338),上海市浦江人才计划(06PJ14121). |
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| High mobility group box chromosomal protein 1 promotes IL-18 production and IL-18 receptor expression in macrophages |
| QIN Yang-hua1,DAI Sheng-ming2*,SHEN Qian1 |
| (1.Department of Laboratory Diagnosis,Changhai Hospital,Second Military Medical University,Shanghai 200433,China;2.Department of Rheumatology and Immunology,Changhai Hospital,Second Military Medical University,Shanghai 200433) |
| Abstract: |
| Objective:To investigate whether high mobility group box chromosomal protein 1(HMGB1) can activate macrophages to secrete IL-18.Methods: Mouse peritoneal macrophages were cultured with HMGB1 for indicated period, then the mRNA and protein expression of IL-18 and IL-18 receptors were examined by real-time PCR, ELISA, and flow cytometric analysis. Toll-like receptor（TLR）2 and 4 agonists (1 μg/ml Pam3Cys or 100 ng/ml LPS) were used as parallel controls.Results: Two hours after culture with HMGB1(100 ng/ml), IL-18 mRNA expression was greatly increased. The expression of IL-18 protein was also greatly increased 24 h after culture with HMGB1, and the expression of IL-18R was slightly up-regulated. Pam3Cys (1 μg/ml) and LPS(100 ng/ml) could promote the expression of IL-18 at both mRNA and protein levels in the macrophages, and could up-regulate IL-18 receptors. Conclusion: HMGB1 can directly activate macrophages to secrete IL-18 and to express IL-18 receptor, suggesting that IL-18 may mediate the proinflammatory activity of HMGB1. |
| Key words: rheumatoid arthritis high mobility group box chromosomal protein 1 macrophages interleukin-18 |
