Anti-inflammatory effects of differential molecular weight Hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation

BACKGROUND: The biological functions of Hyaluronic acid are related to its molecular weight and binding to its receptor, Toll-like receptor4 (TLR4) or CD44. Recent studies have shown that low-molecular-weight Hyaluronic acid (LMW-HA) exhibits proinflammatory effects, while high-molecular-weight Hyaluronic acid (HMW-HA) functions as an anti-inflammatory factor. UVB-induced epidermal inflammation is mainly mediated by endogenous molecules, such as damage-associated molecular patterns (DAMPs), that cause severe skin damage by activating TLR signaling pathways. OBJECTIVE: Since both LMW- and HMW-HA have inhibitory functions on TLR-mediated macrophage inflammation, HA is assumed to suppress UVB-induced DAMP-mediated inflammation in the skin. In this study, both Ultra- low-molecular-weight Hyaluronic acid (uLMW-HA) and HMW-HA were found to inhibit UVB-induced keratinocyte inflammation. METHODS: irradiation. Secreted protein levels were determined with ELISA kits. Expression levels of proteins downstream of TLR4 were detected by Simple Western system. RESULTS: By competitively binding to TLR4, uLMW-HA downregulated Calprotectin-induced TRAF6 expression, which might be the direct process by which uLMW-HA decreased UVB-induced IL-6 secretion. Reduced CD44 variant (CD44v) expression in keratinocytes attenuated the inhibitory effect of both uLMW-HA and HMW-HA on UVB-induced inflammation, which indicated the involvement of CD44v in HA-regulated anti-inflammatory activity. CONCLUSION: Overall, this research indicates that Hyaluronic acid is more than a moisturizer; it is also a biologically effective material that can prevent the excessive skin inflammation caused in daily life, especially in the late stages after sunburn.