Baicalein inhibits IL-1β- and TNF-α-induced inflammatory cytokine production from human mast cells via regulation of the NF-κB pathway

BACKGROUND Human mast cells are multifunctional cells capable of a wide variety of inflammatory responses. Baicalein (BAI), isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have anti-inflammatory effects. We examined its effects and mechanisms on the expression of inflammatory cytokines in an IL-1beta- and TNF-alpha-activated human mast cell line, HMC-1. METHODS HMC-1 cells were stimulated either with IL-1beta (10 ng/ml) or TNF-alpha (100 U/ml) in the presence or absence of BAI. We assessed the expression of IL-6, IL-8, and MCP-1 by ELISA and RT-PCR, NF-kappaB activation by electrophoretic mobility shift assay (EMSA), and IkappaBalpha activation by Western blot. RESULTS BAI (1.8 to 30 muM) significantly inhibited production of IL-6, IL-8, and MCP-1 in a dose-dependent manner in IL-1beta-activated HMC-1. BAI (30 muM) also significantly inhibited production of IL-6, IL-8, and MCP-1 in TNF-alpha-activated HMC-1. Inhibitory effects appear to involve the NF-kappaB pathway. BAI inhibited NF-kappaB activation in IL-1beta- and TNF-alpha-activated HMC-1. Furthermore, BAI increased cytoplasmic IkappaBalpha proteins in IL-1beta- and TNF-alpha-activated HMC-1. CONCLUSION Our results showed that BAI inhibited the production of inflammatory cytokines through inhibition of NF-kappaB activation and IkappaBalpha phosphorylation and degradation in human mast cells. This inhibitory effect of BAI on the expression of inflammatory cytokines suggests its usefulness in the development of novel anti-inflammatory therapies.