TY - JOUR ID - 20238 TI - 6-O-angeloylplenolin inhibits anti-IgE-stimulated human mast cell activation via suppressing calcium influx and ERK phosphorylation JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Yu, Yangyang AU - Lin, Dongxu AU - Liu, Zhenyu AU - Fang, Ran AU - Zheng, Siman AU - Cheng, Yongxian AU - Huang, Zhong AU - Ng, Chun Wai AU - Lau, Hang Yung Alaster AD - Shenzhen University Health Science Center, Shenzhen, China AD - Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China AD - GI Division, Shenzhen University General Hospital, Shenzhen, China AD - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China Y1 - 2022 PY - 2022 VL - 25 IS - 5 SP - 629 EP - 634 KW - 6-O-angeloylplenolin KW - Allergy KW - Inflammation KW - Mast cell KW - SKP1 inhibitor DO - 10.22038/ijbms.2022.64132.14120 N2 - Objective(s): Mast cells are important immune cells that primarily localize in the interface between the host and external environment, and protect us from pathogen infection. However, they are also involved in the pathology of allergic diseases such as asthma and atopic dermatitis. A novel S phase kinase-associated protein 1 (SKP1) inhibitor 6-O-angeloylplenolin (6-OAP), was studied with its potential ability to alleviate the anti-IgE-induced inflammatory responses of primary human cultured mast cells (HCMCs) and LAD2 cell line. Materials and Methods: We isolated the HCMCs from the buffy coat of voluntary blood donors. The effects of 6-OAP on mast cell activation were evaluated by measuring degranulation, cytokine release, migration, calcium influx, and ERK phosphorylation using spectro-fluorescence assay, multiplex cytometric bead assay/ELISA, migration assay, Fluo-4 calcium flux assay, and western blot, respectively. Results: It was found that 6-OAP exerted anti-inflammatory effects on human mast cells by dose-dependently suppressing the anti-IgE-mediated degranulation and release of cytokines such as proinflammatory cytokines (IL-8 and TNF-α), growth factors (GM-CSF, VEGF, and FGF), and chemokines (CCL2 and CCL3) in HCMC and LAD2 cells. It also suppressed the migration of immature HCMCs induced by CXCL12. Moreover, the process of calcium influx and ERK phosphorylation in activated HCMC cells were inhibited by 6-OAP administration. Conclusion: Our results showed that 6-OAP inhibited anti-IgE-induced inflammatory responses of human mast cells via suppressing calcium influx and ERK phosphorylation. UR - https://ijbms.mums.ac.ir/article_20238.html L1 - https://ijbms.mums.ac.ir/article_20238_e1b5a1e3f6f1f1671260cc973b7b0a2e.pdf ER -