Serum amyloid A1 secreted from UV ‐irradiated keratinocytes induces matrix metalloproteinase‐1 in fibroblasts through toll‐like receptor 4

Ultraviolet ( UV ) irradiation on skin triggers photoageing‐related phenotypes such as formation of wrinkles. UV ray upregulates matrix metalloproteinase‐1 ( MMP ‐1), which in turn degrades extracellular matrix proteins, mostly collagens. Serum amyloid A1 ( SAA 1) is an acute‐phase protein of which plasma concentration increases in response to inflammation. Although the expression of SAA 1 in the skin was reported, its function in the skin is yet to be studied. In this research, we found that the expression of SAA 1 was increased in acute UV ‐irradiated buttock skin and photoaged forearm skin in vivo . UV irradiation also increased SAA 1 in normal human epidermal keratinocytes ( NHEK ), and treatment of recombinant human SAA 1 (rh SAA 1) induced MMP ‐1 in normal human dermal fibroblasts ( NHDF ) but not in NHEK . Next, we demonstrated that NHDF treated with UV ‐irradiated keratinocyte‐conditioned media showed the increased MMP ‐1 expression; however, this increase of MMP ‐1 in NHDF was inhibited by knockdown of SAA 1 in NHEK . In addition, knockdown of Toll‐like receptor 4 ( TLR 4) inhibited rh SAA 1‐induced MMP ‐1 expression in NHDF . Taken together, our data showed that UV ‐induced SAA 1 production in NHEK , and this secreted SAA 1 induced MMP ‐1 expression in NHDF in a paracrine manner through TLR 4 signalling pathway. Therefore, our results suggest that SAA 1 can be a potential mediator for UV ‐induced MMP ‐1 expression in human skin.