18β-Glycyrrhetic Acid Inhibits Immune Activation Triggered by HMGB1, a Pro-inflammatory Protein Found in the Tear Fluid during Conjunctivitis and Blepharitis
18β-Glycyrrhetic Acid Inhibits Immune Activation Triggered by HMGB1, a Pro-inflammatory Protein Found in the Tear Fluid during Conjunctivitis and Blepharitis
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DOI：
10.3109/09273948.2010.538121
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发表时间：
2011-06-01
影响因子：
3.3
通讯作者：
Chiarugi, Alberto
中科院分区：
文献类型：
--
作者：
Cavone, Leonardo;Muzzi, Mirko;Chiarugi, Alberto
目的：高迁移率蛋白是染色质结合因子，在核稳态中起关键作用。有证据表明，细胞外释放的高迁移率组框1蛋白（HMGB1）作为细胞因子，促进炎症和疾病的发病。HMGB1释放发生在眼内炎或葡萄膜视网膜炎。方法：对不同外眼炎性疾病患者泪液中HMGB1的表达情况进行研究。结果：数据显示，HMGB1含量在对照组泪液中接近检出限，但在结膜炎或睑缘炎患者泪液中含量高（约15倍）。作者还报道，18 β -甘草酸损害抗体对HMGB1的识别，表明与该蛋白直接结合。因此，在原代培养的人巨噬细胞中，18 β - β -甘草酸可以阻止hmgb1依赖性COX2的表达和簇的形成。结论：综上所述，这些发现表明HMGB1参与了外眼炎症性疾病，而18 β -甘草酸可能清除该蛋白并抑制其有害作用。
Purpose: High-mobility group proteins are chromatin-binding factors with key roles in nuclear homeostasis. Evidence indicates that extracellularly released high-mobility group box 1 protein (HMGB1) behaves as a cytokine, promoting inflammation and disease pathogenesis. HMGB1 release occurs during endophtalmitis or uveoretinitis.Methods: The authors investigated the presence of HMGB1 in tear fluid of patients with different inflammatory disorders of the external eye.Results: Data demonstrate that HMGB1 content is close to detection limit in tears of control subjects but highly increased (about 15-fold) in patients with conjunctivitis or blepharitis. The authors also report that 18 beta beta-glycyrrhetic acid impairs antibody recognition of HMGB1, suggesting direct binding to the protein. Accordingly, 18 beta beta-glycyrrhetic acid prevented HMGB1-dependent COX2 expression and cluster formation in primary cultures of human macrophages.Conclusion: Together, these findings suggest that HMGB1 contributes to inflammatory disorders of the external eye, and 18 beta beta-glycyrrhetic acid may scavenge the protein and inhibit its detrimental effects.