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

Impairment of human neural crest cell migration by prolonged exposure to interferon-beta.
Arch Toxicol. 2017 Apr 01;:
Authors: Pallocca G, Nyffeler J, Dolde X, Grinberg M, Gstraunthaler G, Waldmann T, Rahnenführer J, Sachinidis A, Leist M
Abstract
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 t...

Source: Archives of Toxicology - April 1, 2017 Category: Toxicology Authors: Pallocca G, Nyffeler J, Dolde X, Grinberg M, Gstraunthaler G, Waldmann T, Rahnenführer J, Sachinidis A, Leist M Tags: Arch Toxicol Source Type: research