The contact allergen nickel sensitizes primary human endothelial cells and keratinocytes to TRAIL-mediated apoptosis.

ABSTRACT: Primary endothelial cells are fully resistant to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we demonstrate that certain environmental conditions, such as exposure to the widespread allergen nickel, can dramatically increase the susceptibility of naturally resistant primary endothelial cells or keratinocytes to TRAIL-induced apoptosis. While nickel treatment increased surface expression of the apoptosis-inducing TRAIL receptors TRAIL-R1 and TRAIL-R2, it also up-regulated the apoptosis-deficient TRAIL-R4, suggesting that modulation of TRAIL receptor expression alone is unlikely to fully account for the dramatic sensitization effect of nickel. Further analysis of candidate mediators revealed that nickel strongly repressed c-FLIP at mRNA and protein levels. Accordi

SUBMITTER: Schmidt M 

PROVIDER: S-EPMC3829037 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature