Hyaluronan Oligosaccharides Improve Rosacea-Like Phenotype through Anti-Inflammatory and Epidermal Barrier-Improving Effects

Rosacea is a common skin disease associated with increased expression of cathelicidin, kallikrein 5 (KLK5), toll-like receptor (TLR) 2, and abnormal barrier function. Recently, it was reported that hyaluronan (HA) could influence immune function via various receptors and HA oligosaccharides (oligo-HAs) could suppress TLR-dependent cytokine expression. We investigated if oligo-HAs could influence on inflammation and epidermal barrier induced by LL-37, which had a major role in rosacea. We cultured normal human keratinocytes and treated them with LL-37 and oligo-HAs or the LL-37 alone. A rosacea-like BALB/c mouse model injected with LL-37 was used to determine the role of oligo-HAs in rosacea . Interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α release was suppressed when keratinocytes were co-treated with oligo-HAs and LL-37 compared with keratinocytes treated with LL-37 only. Treatment with oligo-HAs resulted in decreased transepidermal water loss as well as improved redness. Decreased inflammatory cell infiltration, IL-17A and KLK5 expression and increased CD44 and filaggrin expression were also noted. Our findings suggest that oligo-HA improves rosacea-like phenotype through anti-inflammatory and epidermal barrier improving effect.