Open AccessDifferential regulation of nuclear factor‐kappa B subunits on epidermal keratinocytes by ultraviolet B and tacrolimus
Author(s) -
Wu ChingShuang,
Lan ChengChe E.,
Kuo HsuanYu,
Chai CheeYin,
Chen WanTzu,
Chen GwoShing
Publication year - 2012
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2012.04.023
Subject(s) - p50 , nf κb , transcription factor , nfkb1 , protein subunit , downregulation and upregulation , iκbα , ultraviolet b , medicine , keratinocyte , cancer research , immunohistochemistry , inflammation , microbiology and biotechnology , immunology , in vitro , biology , biochemistry , gene , dermatology
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.