Solar-Simulated Ultraviolet Radiation Induces Abnormal Maturation and Defective Chemotaxis of Dendritic Cells

Mittelbrunn, Marı́a; Tejedor, Reyes; Fuente, Hortensia de la; García-López, María Ángeles; Ursa, Ángeles; Peñas, Pablo F.; García‐Diez, Amaro; Alonso-Lebrero, José Luis; Pivel, J.P.; González, Salvador; González‐Amaro, Roberto; Sánchez-Madrid, Francisco

doi:10.1111/j.0022-202x.2005.23824.x

Cited by 29 publications

(24 citation statements)

References 35 publications

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“…A 10–15% cytotoxicity was induced at 4 J/cm 2 (UV induced apoptosis, see Timares et al [21]). This is similar to the results published by Mittelbrunn et al [22] who reported a partial maturation of PDMDCs and approx. 33% cytotoxicity after irradiation with 5 J/cm 2 UVA and 0.4 J/cm 2 UVB generated by a xenon solar simulator.…”

Section: Discussionsupporting

confidence: 92%

A Novel In Vitro Method for the Detection and Characterization of Photosensitizers

et al. 2010

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Photoactivation and binding of photoactive chemicals to proteins is a known prerequisite for the formation of immunogenic photoantigens and the induction of photoallergy. The intensive use of products and the availability of new chemicals, along with an increasing exposure to sun light contribute to the risk of photosensitizing adverse reactions. Dendritic cells (DC) play a pivotal role in the induction of allergic contact dermatitis. Human peripheral blood monocyte derived dendritic cells (PBMDC) were thus perceived as an obvious choice for the development of a novel in vitro photosensitization assay using the modulation of cell surface protein expression in response to photosensitizing agents. In this new protocol, known chemicals with photosensitizing, allergenic or non-allergenic potential were pre-incubated with PBMDCs prior to UVA irradiation (1 J/cm2). Following a 48 h incubation, the expression of the cell surface molecules CD86, HLA-DR and CD83 was measured by flow cytometry. All tested photosensitizers induced a significant and dose-dependent increase of CD86 expression after irradiation compared to non-irradiated controls. Moreover, the phototoxicity of the chemicals could also be determined. In contrast, (i) CD86 expression was not affected by the chosen irradiation conditions, (ii) increased CD86 expression induced by allergens was independent of irradiation and (iii) no PBMDC activation was observed with the non-allergenic control. The assay proposed here for the evaluation of the photoallergenic potential of chemicals includes the assessment of their allergenic, phototoxic and toxic potential in a single and robust test system and is filling a gap in the in vitro photoallergenicity test battery.

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Section: Discussionsupporting

confidence: 92%

A Novel In Vitro Method for the Detection and Characterization of Photosensitizers

et al. 2010

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“…Human monocyte-derived DCs were purified from buffy coats obtained from 3 healthy donors and irradiated with 3.7 J/cm 2 UVA+0.3 J/cm 2 UVB, using a solar simulator. This irradiation dose induces the secretion of TNF-alpha and modifies the expression of several DC surface receptors without causing significant hypodiploidy [14]. Statistical analyses of gene expression values of non-irradiated versus irradiated DC, revealed the modulation of 64 annotated genes with p<0.05.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, several groups have reported the effect of solar-simulated UV radiation on the phenotype and function of human monocyte-derived DCs. Solar-simulated UV radiation results in defective DC maturation and an anomalous migratory phenotype [11], [14]. However, gene expression changes induced in DCs in response to UVA/UVB exposure have not been systematically examined.…”

Section: Introductionmentioning

confidence: 99%

Identification of Genes Responsive to Solar Simulated UV Radiation in Human Monocyte-Derived Dendritic Cells

et al. 2009

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Ultraviolet (UV) irradiation has profound effects on the skin and the systemic immune system. Several effects of UV radiation on Dendritic cells (DCs) functions have been described. However, gene expression changes induced by UV radiation in DCs have not been addressed before. In this report, we irradiated human monocyte-derived DCs with solar-simulated UVA/UVB and analyzed regulated genes on human whole genome arrays. Results were validated by RT-PCR and further analyzed by Gene Set Enrichment Analysis (GSEA). Solar-simulated UV radiation up-regulated expression of genes involved in cellular stress and inflammation, and down-regulated genes involved in chemotaxis, vesicular transport and RNA processing. Twenty four genes were selected for comparison by RT-PCR with similarly treated human primary keratinocytes and human melanocytes. Several genes involved in the regulation of the immune response were differentially regulated in UVA/UVB irradiated human monocyte-derived DCs, such as protein tyrosine phosphatase, receptor type E (PTPRE), thrombospondin-1 (THBS1), inducible costimulator ligand (ICOSL), galectins, Src-like adapter protein (SLA), IL-10 and CCR7. These results indicate that UV-exposure triggers the regulation of a complex gene repertoire involved in human-DC–mediated immune responses.

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“…When high dose of UV was irradiated (as used in this study), apoptosis or cell damage instead of maturation was induced on skin dendritic cells [4,28,29]. Using Western-blotting analysis and the experiments using a specific inhibitor for p38 MAPK, it is clarified that apoptosis of MoDC is mediated at least partly by p38 MAPK [4].…”

Section: Discussionmentioning

confidence: 91%

EGFR activation confers protections against UV-induced apoptosis in cultured mouse skin dendritic cells

Cao

Lü

Jiang

et al. 2008

Cellular Signalling

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Ultraviolet radiation (UV) induces apoptosis and functional maturation in skin dendritic cells (DCs). However, the molecular mechanisms through which UV activates DCs have not been thoroughly investigated. In this study, we examined the mechanisms of activation and apoptosis of DC after UV irradiation by focusing on epidermal growth factor receptor (EGFR). Our previous studies have demonstrated that in addition to cognate ligands, EGFR is also activated by UVB irradiation in cultured human skin keratinocytes in vitro and in human skin in vivo. We found for the first time in this study that UV also induces EGFR activation in cultured mouse skin DCs (XS 106 cell line) as well as mouse monocyte-derived dendritic cells (MoDCs). Pharmacological inhibition of EGFR tyrosine kinase significantly inhibits UV-induced ERK, p38, and JNK MAP kinases, and their effectors, transcription factors c-Fos and c-Jun. Inhibition of EGFR also suppresses UV-induced activation of PI3K/AKT/mTOR/S6K and NF-κB signal transduction pathways. Our data demonstrated that UV induces LKB1/AMPK pathway, also dependent on EGFR trans-activation. We further observed that MAPK, LKB1/AMPK, PI3K/AKT/mTOR/S6K as well as NF-κB activation are impaired in EGFR−/− cells compared to wide type MEF cells after UV radiation. Taken together, we conclude that UV induces multiple signaling pathways mediated by EGFR trans-activation leading to possible maturation, apoptosis and survival, and EGFR activation protects against UVinduced apoptosis in cultured mouse dendritic cells.

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Solar-Simulated Ultraviolet Radiation Induces Abnormal Maturation and Defective Chemotaxis of Dendritic Cells

Cited by 29 publications

References 35 publications

A Novel In Vitro Method for the Detection and Characterization of Photosensitizers

A Novel In Vitro Method for the Detection and Characterization of Photosensitizers

Identification of Genes Responsive to Solar Simulated UV Radiation in Human Monocyte-Derived Dendritic Cells

EGFR activation confers protections against UV-induced apoptosis in cultured mouse skin dendritic cells

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