Dietary supplementation of n-3 PUFAs ameliorates LL37-induced rosacea-like skin inflammation via inhibition of TLR2/MyD88/NF-κB pathway

Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and neurovascular system and treatments for rosacea are challenging. N-3 polyunsaturated fatty acids (PUFAs), one of essential fatty acids, are needed for health maintenance and exert anti-inflammation and immunomodulatory effects in a series of cutaneous diseases such as atopic dermatitis and photoaging through dietary supplementation. However, the role of n-3 PUFAs on rosacea remains to be elucidated. In this study, KEGG enrichment analysis and GO analysis indicated that the biological process and signaling pathways, including chemokine signaling pathway, regulated by n-3 PUFAs highly overlapped with those in the pathogenic biological process of rosacea, especially the erythema telangiectasia type. Next, mice were randomized to fed with a customized n-3 PUFAs diet. We showed that n-3 PUFAs ameliorated skin erythema, inhibited dermal inflammatory cell infiltration (mast cells, neutrophils, and CD4 +T cells) and suppressed elevated pro-inflammatory cytokines in LL37-induced rosacea-like mice. Besides, n-3 PUFAs were also verified to repress angiogenesis in LL37-induced mice skin. Further investigation revealed that n-3 PUFAs attenuated LL37-induced inflammation via TLR2/ MyD88/ NF-κB pathway both in mice and in keratinocytes. In conclusion, our findings underscore that dietary supplementation of n-3 PUFAs have the potential to become an efficient and safe clinical therapeutic candidate for rosacea.