Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and interleukin-1alpha gene expression in human keratinocytes.
Benzoyl peroxide (BP) is used as a topical treatment for acne. Besides its anti-bacterial activity, the exact molecular mechanisms underlying its mode of action are not fully understood. In the current study, the effects of BP on cell viability, antioxidant status and, IL-1 and IL-8 gene expression were investigated in HaCaT keratinocytes. Keratinocytes incubated for 24 h with BP exhibited a dose-dependent cytotoxicity at concentrations above 250 microM. Furthermore, in the presence of 300 microM BP about 50% of the cellular vitamin E was depleted within the first 30 min. The intracellular ratio of oxidized to reduced glutathione (GSSG/GSH) was increased significantly starting 6 h after BP treatments indicating that BP reacts rapidly with targets in the cell membrane and more slowly with those in the cytosol. NF-kappaB transactivation was not significantly affected by BP. However, BP treatment of HaCaT keratinocytes resulted in a dose-dependent increase in IL-1alpha gene expression whereas no changes in IL-8 mRNA levels were observed. These results demonstrate that BP induces an inflammatory reaction mediated by oxidative stress by a pathway independent of the redox-sensitive transcription factor NF-kappaB.
Valacchi
G
G
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA. gvalacchi@ucdavis.edu
Rimbach
G
G
Saliou
C
C
Weber
S U
SU
Packer
L
L
D001585:Benzoyl Peroxide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D003877:Dermatitis, Contact / Q000209:etiology; D003879:Dermatologic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000378:metabolism
D003879:Dermatologic Agents; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014810:Vitamin E; D005978:Glutathione; D019803:Glutathione Disulfide; D001585:Benzoyl Peroxide