Prevention of the ultraviolet B-mediated skin photoaging by a nuclear factor kappaB inhibitor, parthenolide.
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 kappaB (NF-kappaB) is activated upon UV irradiation and induces various genes including interleukin-1 (IL-1), tumor necrosis factor alpha (TNFalpha), 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 TNFalpha induced NF-kappaB activation and then produced MMP-1 and bFGF in HaCaT keratinocytes and skin fibroblasts. In this experiment, we examined if parthenolide, an NF-kappaB inhibitor, could block the UVB-mediated skin changes. We found that parthenolide could effectively inhibit the gene expression mediated by NF-kappaB and the production of bFGF and MMP-1 from cells overexpressing p65, a major subunit of NF-kappaB. We also found that parthenolide could inhibit the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin. These findings suggest that NF-kappaB inhibitors should be useful for the prevention of skin photoaging.
Tanaka
Kiyotaka
K
Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Aichi, Japan.
Hasegawa
Junichi
J
Asamitsu
Kaori
K
Okamoto
Takashi
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010957:Plasmids / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology*; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects; D014162:Transfection; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D012717:Sesquiterpenes; D016222:Fibroblast Growth Factor 2; C002669:parthenolide; D008156:Luciferases; D020781:Matrix Metalloproteinase 1