Sodium hyaluronate fragments promote the expression of human beta-defensin 2 in the skin to alleviate Staphylococcus aureus infection

Background The skin serves as a critical barrier against pathogens and infections, and its microbiome plays a vital role in maintaining immune homeostasis. Human beta-defensin 2 (HBD2) is an antimicrobial peptide essential for skin immunity. While hyaluronic acid (HA) is widely used in pharmaceuticals and cosmetics, its antimicrobial properties against Staphylococcus aureus ( S. aureus ) infection in skin cells remain understudied. This study investigates the role of low molecular weight HA (0.8 kDa) in promoting HBD2 expression and its potential to combat S. aureus infection. Materials and Methods HA was synthesized and tested for its ability to induce HBD2 expression in human keratinocytes and reconstructed epidermal skin equivalents. The antibacterial activity of HA was evaluated using S. aureus infection models, while the underlying signaling pathways were explored through Western blotting and inhibitor studies. Inflammatory cytokines (TNF-α and IL-6) were quantified using ELISA. Results HA (0.8 kDa) significantly upregulated HBD2 expression in keratinocytes and reconstructed skin models through the TLR2/4-MyD88-ERK signaling pathway. HA treatment reduced S. aureus infection and suppressed the secretion of pro-inflammatory cytokines TNF-α and IL-6. In reconstructed epidermal skin equivalents, HA enhanced structural integrity and endogenous antimicrobial activity, further confirming its potential as an anti-inflammatory and antibacterial agent. Conclusion Low molecular weight HA (0.8 kDa) promotes HBD2 expression and exhibits antibacterial and anti-inflammatory effects against S. aureus infection. These findings highlight HA's potential applications in skincare products for enhancing innate immunity and managing skin infections.