Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings suggest that defects in dermo/epidermal interactions could contribute to BCC susceptibility in NBCCS patients.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01257867
http://hal.upmc.fr/hal-01257867
http://hal.upmc.fr/hal-01257867/document
http://hal.upmc.fr/hal-01257867/file/journal.pone.0145369.pdf
DOI : 10.1371/journal.pone.0145369

Éditeur(s) : HAL CCSD Georg Thieme Verlag
Résumé : International audience
Oil from the nuts of Calophyllum inophyllum, locally called "Tamanu oil" in French Polynesia, was traditionally used for wound healing and to cure various skin problems and ailments. The skin-active effect of "Tamanu oil emulsion" was investigated on human skin cells (keratinocytes and dermal fibroblasts) and showed cell proliferation, glycosaminoglycan and collagen production, and wound healing activity. Transcriptomic analysis of the treated cells revealed gene expression modulation including genes involved in the metabolic process implied in O-glycan biosynthesis, cell adhesion, and cell proliferation. The presence of neoflavonoids as bioactive constituents in Tamanu oil emulsion may contribute to these biological activities. Altogether, consistent data related to targeted histological and cellular functions brought new highlights on the mechanisms involved in these biological processes induced by Tamanu oil effects in skin cells.
ISSN: 0032-0943

hal-01592246
https://hal.archives-ouvertes.fr/hal-01592246
DOI : 10.1055/s-0042-108205

Éditeur(s) : HAL CCSD American Society for Investigative Pathology
Résumé : International audience
Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermalinfiltrates of CD45(+) leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1 beta. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients.
ISSN: 0002-9440

hal-01390977
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390977
DOI : 10.1016/j.ajpath.2016.05.012
PUBMED : 27423696

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Due to shallow penetration of millimeter waves (MMW) and convection in liquid medium surrounding cells, the problem of accurate assessment of local MMW heating in in vitro experiments remains unsolved. Conventional dosimetric MMW techniques, such as infrared imaging or fiber optic (FO) sensors, face several inherent limits. Here we propose a methodology for accurate local temperature measurement and subsequent specific absorption rate (SAR) retrieval using microscale thermocouples (TC). SAR was retrieved by fitting the measured initial temperature rise to the numerical solution of an equivalent thermal model. It was found that the accuracy of temperature measurement depends on thermosensor size, that is, the smaller TC, the more accurate the temperature measurement. SAR determined using TC with lead diameters of 25 and 75m demonstrated 98.5% and 80.4% match with computed SAR, respectively. However, both TC provided the same temperature rises in long run (>10min). FO probe failed to measure adequately local heating both for short and long exposures due to the relatively large size of the probe sensor (400m) and time constant (0.6s). Calculated SAR in the cell monolayer was almost two times lower than that in the surrounding liquid. It was shown that the impact of the cell monolayer on heating due to its small thickness (5 to 10m) can be considered as negligible. Moreover, we demonstrated the possibility of accurate measurement of MMW-induced thermal pulses (up to 10 degrees C) using 25m TC. Bioelectromagnetics. 38:11-21, 2017. (c) 2016 Wiley Periodicals, Inc.
ISSN: 0197-8462

hal-01436768
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01436768
DOI : 10.1002/bem.21999
PUBMED : 27571392

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Emerging high data rate wireless communication systems, currently under development, will operate at millimeter waves (MMW) and specifically in the 60 GHz band for broadband short-range communications. The aim of this study was to investigate potential effects of MMW radiation on the cellular endoplasmic reticulum (ER) stress. Human skin cell lines were exposed at 60.4 GHz, with incident power densities (IPD) ranging between 1 and 20 mW/cm(2) . The upper IPD limits correspond to the ICNIRP local exposure limit for the general public. The expression of ER-stress sensors, namely BIP and ORP150, was then examined by real-time RT-PCR. Our experimental data demonstrated that MMW radiations do not change BIP or ORP150 mRNA basal levels, whatever the cell line, the exposure duration or the IPD level. Co-exposure to the well-known ER-stress inducer thapsigargin (TG) and MMW were then assessed. Our results show that MMW exposure at 20 mW/cm(2) inhibits TG-induced BIP and ORP150 over expression. Experimental controls showed that this inhibition is linked to the thermal effect resulting from the MMW exposure. Bioelectromagnetics. 35:444-451, 2014. © 2014 Wiley Periodicals, Inc.
ISSN: 0197-8462

hal-01063910
https://hal.archives-ouvertes.fr/hal-01063910
DOI : 10.1002/bem.21864
PUBMED : 25099539