title: Prevention of the ultraviolet B-mediated skin photoaging by a nuclear factor kappaB inhibitor, parthenolide.
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 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.
authors: Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Aichi, Japan.
authors: Kiyotaka
authors: K
authors: Tanaka
authors: Junichi
authors: J
authors: Hasegawa
authors: Kaori
authors: K
authors: Asamitsu
authors: Takashi
authors: T
authors: Okamoto
mesh_terms: 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
chemical_list: 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