Abstract

The skin photoaging is characterized by keratinocyte hyperproliferation and degradation of collagen fibers, causing skin wrinkling and laxity and melanocyte proliferation that leads to pigmentation. UV is considered to be a major cause of such skin changes. It is well established that nuclear factor κB (NF-κB) is activated upon UV irradiation and induces various genes including interleukin-1 (IL-1), tumor necrosis factor α (TNFα), and matrix metalloprotease-1 (MMP-1). It is also known that basic fibroblast growth factor (bFGF) production is induced by UV and promotes the proliferation of skin keratinocytes and melanocytes. We found that UVB, IL-1, and TNFα induced NF-κB activation and then produced MMP-1 and bFGF in HaCaT keratinocytes and skin fibroblasts. In this experiment, we examined if parthenolide, an NF-κB inhibitor, could block the UVB-mediated skin changes. We found that parthenolide could effectively inhibit the gene expression mediated by NF-κB and the production of bFGF and MMP-1 from cells overexpressing p65, a major subunit of NF-κB. We also found that parthenolide could inhibit the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin. These findings suggest that NF-κB inhibitors should be useful for the prevention of skin photoaging.