Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-alpha/IFN-gamma-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-alpha/IFN-gamma in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-alpha/IFN-gamma-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-kappa B, and p38 MAPK mediate TNF-alpha/IFN-gamma-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-alpha/IFN-gamma-induced phosphorylation of STAT1, NF-kappa B, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-alpha/IFN-gamma-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-kappa B, and p38 MAPK signaling pathways.

Automated summary

This study found that SFII inhibits the expression of TARC, MDC, and CTSS induced by TNF-alpha/IFN-gamma by regulating the STAT1, NF-kappa B, and p38 MAPK signaling pathways.