The Influence of Ultraviolet Light on Immunological Cytotoxicity in the Skin

Norris, David A.; Whang, Ki‐Woong; David-Bajar, Kathleen M.; Bennion, Scott D.

doi:10.1111/j.1751-1097.1997.tb01905.x

Cited by 39 publications

(37 citation statements)

References 112 publications

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“…UVB is a complete carcinogen that is known to act both as a tumor initiator and a tumor promoter (43,59). Exposure of the skin to UVB induces the stereotypic early responses of genes such as c-fos and c-jun (6,26,27,63) and delayed responses, including hyperplasia and skin cancer (21,26,48,72). The induction of the early response genes results from a cascade of signaling events that eventually modulates the activity of specific transcription factors.…”

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confidence: 99%

The UV (Ribotoxic) Stress Response of Human Keratinocytes Involves the Unexpected Uncoupling of the Ras-Extracellular Signal-Regulated Kinase Signaling Cascade from the Activated Epidermal Growth Factor Receptor

Iordanov

Choi

Ryabinina

et al. 2002

Molecular and Cellular Biology

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In mammals, UVB radiation is of biological relevance primarily for the cells of the epidermis. We report here the existence of a UVB response that is specific for proliferating human epidermal keratinocytes. Unlike other cell types that also display a UVB response, keratinocytes respond to UVB irradiation with a transient but potent downregulation of the Ras-extracellular signal-regulated kinase (ERK) signaling cascade. The downregulation of ERK precedes a profound decrease in the steady-state levels of cyclin D1, a mediator of the proliferative action of ERK. Keratinocytes exhibit high constitutive activity of the Ras-ERK signaling cascade even in culture medium lacking supplemental growth factors. The increased activity of Ras and phosphorylation of ERK in these cells are maintained by the autocrine production of secreted molecules that activate the epidermal growth factor receptor (EGFR). Irradiation of keratinocytes increases the phosphorylation of EGFR on tyrosine residues Y845, Y992, Y1045, Y1068, Y1086, Y1148, and Y1173 above the basal levels and leads to the increased recruitment of the adaptor proteins Grb2 and ShcA and of a p55 form of the regulatory subunit of the phosphatidylinositide 3-kinase to the UVB-activated EGFR. Paradoxically, however, UVB causes, at the same time, the inactivation of Ras and a subsequent dephosphorylation of ERK. By contrast, the signaling pathway leading from the activated EGFR to the phosphorylation of PKB/Akt1 is potentiated by UVB. The UVB response of keratinocytes appeared to be a manifestation of the more general ribotoxic stress response inasmuch as the transduction of the UVB-generated inhibitory signal to Ras and ERK required the presence of active ribosomes at the time of irradiation.

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confidence: 99%

The UV (Ribotoxic) Stress Response of Human Keratinocytes Involves the Unexpected Uncoupling of the Ras-Extracellular Signal-Regulated Kinase Signaling Cascade from the Activated Epidermal Growth Factor Receptor

Iordanov

Choi

Ryabinina

et al. 2002

Molecular and Cellular Biology

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“…The effects of UVB (290-320 nm) radiation on human skin can be seen as acute (sunburn and inflammation) (Grassen and van Loveren [2]) or chronic (photoaging and skin cancer) ( [2]; Tebbe et al [3]; Deliconstantinos et al [4]). The acute effects of UVB are thought to be mediated by cytokine production leading to cell death (early apoptosis) (Petit-Frere et al [5]; Norris et al [6]; Gniadecki et al [7]; Corsini et al [8]). …”

Section: Introductionmentioning

confidence: 99%

Combining three in vitro assays for detecting early signs of UVB cytotoxicity in cultured human skin fibroblasts

Khalil¹

2006

WIT Transactions on Biomedicine and Health, Vol 10

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The aim of this study was to determine the most sensitive approach for detecting the early signs of UVB-induced cellular damage using human skin fibroblasts. UVB-induced cell damage was assessed immediately and 24 h post irradiation using 3 in vitro colorimetric assays: neutral red (NR); 5-(3-carboxymethoxyphenyl)-2-(4.5-dimethylthiazolyl)-3-(4-sulphonyl) MTS; and (iii) LDH enzyme release. A good correlation was observed immediately post exposure between the MTS and NR in measuring damage levels, but was lost 24 h post exposure. This loss of correlation was the result of delayed expression of lysosomal damage and led to investigating cell membrane damage using LDH cell leakage assay. LDH levels observed immediately post UVB irradiation indicated significant LDH release at exposure doses of 2.2 and 2.8 J/cm 2 , while LDH release reported 24 h post exposure was recorded for doses as low as 0.70 J/cm 2 . The data reported in this paper indicated that cell viability and damage were significantly affected in a dose dependent manner as a result of exposure doses. The assays used displayed different sensitivities in detecting damage with the earliest signs of cellular UVB damage best-measured 24 h following exposure using the LDH assay. Furthermore UVB contributed to denaturing the cellular LDH released during irradiation. Therefore the use of LDH cytotoxicity based assays with UVB exposure must be considered with extreme care.

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“…Diversos estudos têm demonstrado tanto in vivo quanto in vitro os efeitos deletérios da radiação ultravioleta nos pacientes com LE (Norris et al, 1997;Sontheimer et al, 1997). Os diferentes espectros, tanto UVA quanto UVB, têm um importante papel na iniciação e na exacerbação das lesões cutâneas do LE Kuhn et al, 2001;Lee, 2008) e potencializam sintomas sistêmicos da doença ).…”

Section: Radiação Ultravioletaunclassified

“…3.6 Radiação ultravioleta e lúpus eritematoso Na literatura, diversos trabalhos demonstram que a radiação ultravioleta é um importante mecanismo de indução da lesão de LE (Norris et al, 1997;Rosenbaum et al, 2005;.…”

Section: Radiação Ultravioletaunclassified

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Manifestações orais do lúpus eritematoso: padrão das citocinas do infiltrado inflamatório

Marques¹

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Dedicatória DedicatóriaAo meu marido, Telmo, pelo seu enorme amor e dedicação a mim, pelo incentivo e apoio incondicional a todos os meus sonhos e pela satisfação com conquistas minhas mais do que com as próprias.Aos meus filhos, Gustavo e Giulia, pelo carinho, incentivo e compreensão pelas frequêntes ausências.À minha mãe, Lourdes, por ter me ensinado a prezar a busca pelo conhecimento e por sua dedicação, estímulo e presença, com seu amor incondicional, em todos os momentos da minha vida.Ao meu pai, Jarbas, pelos bons momentos que convivemos.Ao meu irmão, Jarbas Eduardo, antes de tudo um amigo, grande incentivador do meu crescimento profissional.Aos meus cunhados, Thiers, Simone e Maria Alice, que tornam a minha família ainda melhor. Agradecimentos AgradecimentosAo meu orientador, Prof. Dr. Marcello Menta S. Nico, por sua condução firme, segura e participativa, com contribuições e ensinamentos valiosos em todos os momentos do desenvolvimento deste estudo, a quem aprendi a admirar e respeitar por sua sabedoria e dedicação. Agradeço pelo privilégio de ter trabalhado ao seu lado. À Profª. Dra. Sílvia Vanessa Lourenço, pela profissional dedicada, solícita, participativa, um exemplo a ser admirado e seguido. Devo, principalmente ao seu incentivo, apoio, ajuda e ensinamentos, a realização deste estudo. À Profª. Dra. Miriam Nacami Sotto, pela confiança, incentivo e ajuda para que este estudo pudesse ser realizado. À Dona Eli Maria, pela eficiência e competência na resolução de nossas dúvidas.

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The Influence of Ultraviolet Light on Immunological Cytotoxicity in the Skin

Cited by 39 publications

References 112 publications

The UV (Ribotoxic) Stress Response of Human Keratinocytes Involves the Unexpected Uncoupling of the Ras-Extracellular Signal-Regulated Kinase Signaling Cascade from the Activated Epidermal Growth Factor Receptor

The UV (Ribotoxic) Stress Response of Human Keratinocytes Involves the Unexpected Uncoupling of the Ras-Extracellular Signal-Regulated Kinase Signaling Cascade from the Activated Epidermal Growth Factor Receptor

Combining three in vitro assays for detecting early signs of UVB cytotoxicity in cultured human skin fibroblasts

Manifestações orais do lúpus eritematoso: padrão das citocinas do infiltrado inflamatório

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