title: Differential regulation of nuclear factor-kappa B subunits on epidermal keratinocytes by ultraviolet B and tacrolimus.
abstract: Modulation of nuclear factor-kappa B (NF-κB) expression has important clinical implications including anti-inflammation. Recently, we have shown that direct regulation of NF-κB/p65 subunit may account for tacrolimus ointment's remarkable clinical efficacy on treating inflammatory dermatoses. However, NF-κB is a dimeric transcription factor formed by hetero- or homodimeration of the five Rel family proteins. The complete operational scheme of different NF-κB subunits remains obscure. It has been shown that homodimers consist of NF-κB/p50 may serve an inhibitory role in suppressing inflammation while dimers consisting of NF-κB/p65 activate inflammatory pathway. Our current study aimed to explore the effects of ultraviolet B (UVB) on epidermal keratinocytes in terms of specific NF-κB subunits NF-κB/p50 and NF-κB/p65. Additionally, the effects of tacrolimus on differential regulation of NF-κB subunits of UVB irradiated keratinocytes were also investigated. Our result showed that UVB sequentially regulated the activities of different subunits of NF-κB: the activity of NF-κB/p50 was downregulated in the early stage (6 hours), followed by upregulation of NF-κB/p65 in the later stage (12 hours). The results from immunofluorescence, immunocytochemical, and immunohistochemical analyses indicated that the nuclear expression of NF-κB/p50 could be seen constitutively while the nuclear expression of NF-κB/p65 could only be seen after UVB irradiation. Furthermore, treatment with tacrolimus didn't affect the nuclear activation and translocation of NF-κB/p50, while the UVB induced NF-κB/p65 nuclear expression was suppressed by tacrolimus. In summary, we have shown that UVB irradiation sequentially regulated different NF-κB subunits. The clinical efficacy of tacrolimus may be attributed to its specific regulatory effect on NF-κB/p65 but not NF-κB/p50 of the NF-κB pathway.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-Shuang
authors.initials: CS
authors.lastname: Wu
authors.forename: Cheng-Che E
authors.initials: CC
authors.lastname: Lan
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Kuo
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Wan-Tzu
authors.initials: WT
authors.lastname: Chen
authors.forename: Gwo-Shing
authors.initials: GS
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000528:radiation effects*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D021381:Protein Transport; D016559:Tacrolimus / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D051996:Transcription Factor RelA; D016559:Tacrolimus