740 Serum Amyloid A1 is induced by UV irradiation and detected by toll-like receptor 4 to cause skin inflammation

Abstract

Cutaneous inflammation induced by UV irradiation has been well documented clinically. However, despite many previous efforts, it is not fully understood which molecules mediate this inflammatory response. Our recent study found that serum amyloid A1 (SAA1) was increased in UV-irradiated human skin. Since SAA1 has been reported to exert proinflammatory effect, this finding implicates SAA1 as a mediator in UV-induced cutaneous inflammation. Here, we demonstrated that the expression of SAA1 was increased by acute UV irradiation in mouse skin in vivo. Intradermal injection of recombinant mouse SAA1 caused inflammation and induced IL-1β and IL-6 in mouse skin in vivo. Correspondingly, treatment of recombinant human SAA1 (rhSAA1) induced IL-1β, IL-6, and IL-8 in primary normal human dermal fibroblasts (NHDFs). In addition, knockdown of Toll-like receptor 4 (TLR4) or blocking of NF-κB signaling pathway attenuated rhSAA1-induced proinflammatory cytokine expressions in NHDFs. Taken together, our data showed that SAA1 was produced by UV irradiation and induced inflammation in mouse skin in vivo and that SAA1 induced proinflammatory cytokines in NHDFs through TLR4/NF-κB signaling pathway. Therefore, our results suggest that SAA1 can be a potential mediator for UV irradiation-induced cutaneous inflammation.