A novel strategy for development of glucocorticoids through non-genomic mechanism

作者：Zhou Jian; Li Min; Sheng Chun Quan; Liu Lei; Li Zhen; Wang Yan; Zhou Jiang Rui; Jing Zai Ping; Chen Yi Zhang; Jiang Chun Lei^*

来源：Cellular and Molecular Life Sciences, 2011, 68(8): 1405-1414.

DOI：10.1007/s00018-010-0526-0

• Glucocorticoids
• Non-genomic
• Neutrophil
• Allergy
• Mast cells

Glucocorticoids (GCs) are routinely believed to take effect through genomic mechanisms, which are also largely responsible for GCs'; side effects. Beneficial non-genomic effects of GCs have been reported as being independent of the genomic pathway. Here, we synthesized a new type of GCs, which took effect mainly via non-genomic mechanisms. Hydrocortisone was conjugated with glycine, lysine and phenylalanine to get a bigger molecular structure, which could hardly go through the cell membrane. Evaluation of the anti-inflammatory efficacy showed that hydrocortisone-conjugated glycine (HG) and lysine could inhibit neutrophil degranulation within 15 min. HG could inhibit IgE-mediated histamine release from mast cells via a non-genomic pathway, and rapidly alleviate allergic reaction. Luciferase reporter assay showed that HG would not activate the glucocorticoid response element within 30 min, which verified the rapid effects independent of the genomic pathway. The work proposes a novel insight into the development of novel GCs, and provides new tools for experimental study on non-genomic mechanisms.

• 出版日期2011-4
• 单位中国人民解放军第二军医大学