Xanthii fructus extract inhibits TNF-α/IFN-γ-induced Th2-chemokines production via blockade of NF-κB, STAT1 and p38-MAPK activation in human epidermal keratinocytes

Abstract

Ethnopharmacological relevanceXanthii fructus (XF) is an herb widely used in medicine for the treatment of a variety of inflammatory pathologies. Chemokines are important mediators of cell migration, and thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well-known typical inflammatory chemokines involved in atopic dermatitis (AD). However, the anti-inflammatory mechanisms of XF have not been elucidated in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT cells. The purpose of this study was to investigate the effect of XF on TNF-α/IFN-γ-induced production of TARC/CCL17 and MDC/CCL22 in HaCaT cells. Materials and methodsHaCaT cells were stimulated by TNF-α/IFN-γ in the presence of XF. TRAC/CCL17 and MDC/CCL22 productions were monitored by ELISA on the cell culture supernatant and by RT-PCR on total RNA extract. We use immunoblotting to analyze the effect of XF on activation of the NF-κB, STAT1 and MAPK pathways. ResultsEthanol extract of XF (EXF) inhibited mRNA expression and production of TARC/CCL17 and MDC/CCL22 induced by TNF-α/IFN-γ in a dose-dependent manner. It also significantly inhibited TNF-α/IFN-γ-induced activation of NF-κB, STAT1 and p38-MAPK. Furthermore, we observed that p38-MAPK contributes to the inhibition of TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 production by blocking NF-κB and STAT1 activation in HaCaT cells. ConclusionsThese results demonstrate that developing therapeutic applications XF for the prevention of inflammatory skin diseases are feasible.