PT  - JOURNAL ARTICLE
AU  - Kiyotaka Tanaka
AU  - Junichi Hasegawa
AU  - Kaori Asamitsu
AU  - Takashi Okamoto
TI  - Prevention of the Ultraviolet B-Mediated Skin Photoaging by a Nuclear Factor κB Inhibitor, Parthenolide
AID  - 10.1124/jpet.105.088674
DP  - 2005 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 624--630
VI  - 315
IP  - 2
4099  - http://jpet.aspetjournals.org/content/315/2/624.short
4100  - http://jpet.aspetjournals.org/content/315/2/624.full
SO  - J Pharmacol Exp Ther2005 Nov 01; 315
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics