UVB-induced association of tumor necrosis factor (TNF) receptor 1/TNF receptor-associated factor-2 mediates activation of Rel proteins

Abstract

Exposure of mammalian skin to UV light results in induced gene transcription, playing a role in inf lammation, immunosuppression, and tumor promotion. One important group of transcription factors induced by UV radiation is composed of members of the Rel͞NF-B family, which are known to play a major role in the transcriptional activation of many genes encoding inf lammatory cytokines, adhesion molecules, and viral proteins. However, the upstream events in the transduction of the UVB signal to Rel protein activity are, as yet, unknown. Here, we provide biochemical evidence that exposure of keratinocytes to UVB causes rapid association of tumor necrosis factor (TNF) receptor 1 with its downstream partner TRAF-2. The functional relevance of this association is demonstrated by experiments showing that expression of a dominant negative TNF receptor 1 or TRAF-2 protein inhibits UVB-induced Rel-dependent transcription. Inclusion of a neutralizing antibody toward TNF␣ has no effect on UVB activation of a Rel-responsive reporter gene. Therefore, UVB-induced activation of Rel proteins via TNF receptor 1, independent of ligand activation, is a key component in the UV response in keratinocytes.

Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin

“…All three of these gene biomarkers were significantly decreased with R-equol and/or racemic equol compared to S-equol. Looking at other aging genes, the FOS (immediate early) biomarker is known to protect against photoaging while TNFRSF1A is involved with UV-induced DNA damage via sun exposure or photoaging (Tobin et al, 1998;Tomicic et al, 2011). The highest levels of FOS gene expression were seen with racemic equol.…”

Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency

“…An initial step in UV-induced photocarcinogenesis is the formation of potentially mutagenic DNA damage in skin cells. In addition, UVB may induce changes in the expression of many genes (Tobin et al, 1998) and trigger the release of various cytokines from human keratinocytes, e.g., IL-6, TNF-a, IL-1, IL-10, and IL-12 (Kondo and Jimbow, 1998;EberleinKonig et al, 1998;Soriani et al, 1999). These cytokines may provide the growth advantages for the initiated or mutant skin cells, which, in turn, enhance the development of skin cancer.…”

Ultraviolet-irradiation-induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1

“…For example, UV-irradiation has been shown to activate NF-kB in enucleated cells (Devary et al, 1993); a ®nding which rules out nuclear DNA damage as a trigger in some of the UV-mediated e ects. Tobin et al (1998), have recently reported that UV activation of Rel/NF-kB appears to occur via TNFR1. UV-induced multimerization and activation of TNFR1 has also been shown and was implicated in UV stimulation of JNK activation (Rosette and Karin, 1996).…”