Berberine Inhibits Eczematous Skin S. aureus-Induced Mast Cell/Basophil Activation and Modulates MAPK-Associated Gene Expression

Abstract

Staphylococcus aureus (S. aureus), a primary exacerbating factor in eczema, remains a prevalent pathogenic public-health threat. The mechanism of mast cell/basophil degranulation in the context of S. aureus-exacerbated eczema remains unclear. We sought to investigate the direct effect of mast cell/basophil activation by S. aureus isolated from patients with severe eczema undergoing topical steroid withdrawal (TSW) and understand the mechanism of berberine (BBR) in inhibiting this activation. Clinical S. aureus strains (N = 8) were isolated from skin swabs of severe eczema patients and confirmed by sequencing. Human basophils (KU812), rat basophils (RBL-2H3) and murine mast cells (MC/9) were pre-treated with BBR for 48 h. and stimulated with heat-killed standard S. aureus- and clinical strains for 45 min, and degranulation was measured. BBR’s molecular-targets on basophils were identified by computational modeling and validated by qRT-PCR. BBR prevented degranulation following standard S. aureus stimulation in KU812, RBL-2H3 and MC/9 cells. BBR dose-dependently inhibited degranulation in KU812. BBR inhibited TNF-α and IL-4 release, and markedly suppressed the expression of FcεR1 (α, β, γ), TNFα, MAPK1, MAPK3, AKT2, CASP9, and CCND1 following standard S. aureus stimulation. BBR dose-dependently inhibited KU812 cell degranulation, markedly reduced TNF-α, IL-4, and MAPK1 and enhanced NFκB1A expression following clinical S. aureus strain stimulation. BBR inhibition of S. aureus-induced KU812 activation was at least associated with inhibition of MAPK-associated gene expression. This study provides novel insights into BBR’s effect in preventing S. aureus and human basophil interaction.