Impairment of human neural crest cell migration by prolonged exposure to interferon-beta

Pallocca, Giorgia; Nyffeler, Johanna; Dolde, Xenia; Grinberg, Marianna; Gstraunthaler, Gerhard; Waldmann, Tanja; Rahnenführer, Jörg; Sachinidis, Agapios; Leist, Marcel

Impairment of human neural crest cell migration by prolonged exposure to interferon-beta

Dateien

Pallocca_1-a0c118cc267243c64.pdfGröße: 5.26 MBDownloads: 541

Datum

2017

Autor:innen

Pallocca, Giorgia

Nyffeler, Johanna

Dolde, Xenia

Grinberg, Marianna

Gstraunthaler, Gerhard

Waldmann, Tanja

Rahnenführer, Jörg

Sachinidis, Agapios

Leist, Marcel

EU-Projektnummer

681002

Projekt

EUToxRisk21

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Archives of Toxicology. 2017, 91(10), pp. 3385-3402. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-017-1966-1

Zusammenfassung

Human cell-based toxicological assays have been used successfully to detect known toxicants, and to distinguish them from negative controls. However, there is at present little experience on how to deal with hits from screens of compounds with yet unknown hazard. As a case study to this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified as a hit during a screen of clinically used drugs in the 'migration inhibition of neural crest' (MINC) assay. Concentration-response studies in the MINC combined with immunocytochemistry and mRNA quantification of cellular markers showed that IFNβ inhibited NCC migration at concentrations as low as 20 pM. The effective concentrations found here correspond to levels found in human plasma, and they were neither cytostatic nor cytotoxic nor did they did they affect the differentiation state and overall phenotype of NCC. Data from two other migration assays confirmed that picomolar concentration of IFNβ reduced the motility of NCC, while other interferons were less potent. The activation of JAK kinase by IFNβ, as suggested by bioinformatics analysis of the transcriptome changes, was confirmed by biochemical methods. The degree and duration of pathway activation correlated with the extent of migration inhibition, and pharmacological block of this signaling pathway before, or up to 6 h after exposure to the cytokine prevented the effects of IFNβ on migration. Thus, the reduction of vital functions of human NCC is a hitherto unknown potential hazard of endogenous or pharmacologically applied interferons.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

PALLOCCA, Giorgia, Johanna NYFFELER, Xenia DOLDE, Marianna GRINBERG, Gerhard GSTRAUNTHALER, Tanja WALDMANN, Jörg RAHNENFÜHRER, Agapios SACHINIDIS, Marcel LEIST, 2017. Impairment of human neural crest cell migration by prolonged exposure to interferon-beta. In: Archives of Toxicology. 2017, 91(10), pp. 3385-3402. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-017-1966-1

BibTex

@article{Pallocca2017-10Impai-38586,
  year={2017},
  doi={10.1007/s00204-017-1966-1},
  title={Impairment of human neural crest cell migration by prolonged exposure to interferon-beta},
  number={10},
  volume={91},
  issn={0340-5761},
  journal={Archives of Toxicology},
  pages={3385--3402},
  author={Pallocca, Giorgia and Nyffeler, Johanna and Dolde, Xenia and Grinberg, Marianna and Gstraunthaler, Gerhard and Waldmann, Tanja and Rahnenführer, Jörg and Sachinidis, Agapios and Leist, Marcel}
}

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Universitätsbibliographie

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