Protecting skin photoaging by NF-kappaB inhibitor.
The skin photoaging is an inevitable process that occurs in daily life. It ischaracterized by acceralated keratinocyte proliferation and degradation of collagen fibers, causing skin wrinkling and laxity, and melanocyte proliferation that leads to pigmentation. Ultraviolet (UV) is considered to be a major cause of such skin changes. It is well established that nuclear factor kappa B (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 production of basic fibroblast growth factor (bFGF) is induced in skin tissues by UV irradiation and it promotes the proliferation of skin keratinocytes and melanocytes. We found that either UVB, IL-1 or TNFalpha could induce NF-kappaB by activating its signal transduction pathway. The activated NF-kappaB produces MMP-1 and bFGF in skin fibroblasts and human keratinocyte cell line HaCaT. In this experiment, we examined whether parthenolide and magnolol, NF-kappaB inhibitors, could block such UVB-mediated skin changes. We found that either parthenolide or magnolol 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 these NF-kappaB inhibitors could inhibit the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin. These findings suggest that NF-kappaB inhibitors are useful in preventing the skin photoaging.
Tanaka
Kiyotaka
K
Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. tokamoto@med.nagoya-cu.ac.jp
Asamitsu
Kaori
K
Uranishi
Hiroaki
H
Iddamalgoda
Arunasiri
A
Ito
Kenichi
K
Kojima
Hiroyuki
H
Okamoto
Takashi
T
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects* / Q000473:pathology; D014466:Ultraviolet Rays / Q000009:adverse effects
D016328:NF-kappa B