Liang Zheng, Luo Zecheng, Chen Jian, Li Baojie, Li Lin, Shen Chongyang
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Immunobiology. 2022 Mar;227(2):152182. doi: 10.1016/j.imbio.2022.152182. Epub 2022 Feb 3.
IL-4 plays a key role in many human diseases, including allergic asthma, autoimmunity, allergies, and cancer. Therefore, the investigation of small compounds that regulate IL-4 secretion is of great interest for fighting these diseases. Natural flavonoids are useful compounds reported to have therapeutic effects in diseases involving IL-4. This study aimed to investigate small compounds that inhibit the effect of IL-4 with the lowest cell toxicity. We found that Bavachin had the greatest ability to downregulate IL-4 in the spleen of T cells from 4get IL-4-GFP mice. To identify the underlying molecular mechanisms, we found that Bavachin could decrease the IL-4 levels by downregulating the level of Gata-3 expression and STAT6 phosphorylation. These findings reveal the potential use of Bavachin as a tool for selectively controlling diseases involving IL-4 and, more generally, STAT6-dependent responses.
白细胞介素-4在许多人类疾病中发挥关键作用,包括过敏性哮喘、自身免疫性疾病、过敏和癌症。因此,研究调节白细胞介素-4分泌的小分子化合物对于对抗这些疾病具有极大的意义。天然黄酮类化合物是有用的化合物,据报道在涉及白细胞介素-4的疾病中具有治疗作用。本研究旨在研究具有最低细胞毒性的抑制白细胞介素-4作用的小分子化合物。我们发现补骨脂二氢黄酮在4get白细胞介素-4-绿色荧光蛋白小鼠的T细胞脾脏中下调白细胞介素-4的能力最强。为了确定潜在的分子机制,我们发现补骨脂二氢黄酮可以通过下调Gata-3表达水平和STAT6磷酸化来降低白细胞介素-4水平。这些发现揭示了补骨脂二氢黄酮作为一种工具选择性控制涉及白细胞介素-4的疾病以及更普遍的STAT6依赖性反应的潜在用途。