@article{ZannasArlothCarrilloRoaetal.2015,
  author    = {Zannas, Anthony S. and Arloth, Janine and Carrillo-Roa, Tania and Iurato, Stella and R{\"o}h, Simone and Ressler, Kerry J. and Nemeroff, Charles B. and Smith, Alicia K. and Bradley, Bekh and Heim, Christine and Menke, Andreas and Lange, Jennifer F. and Br{\"u}ckl, Tanja and Ising, Marcus and Wray, Naomi R. and Erhardt, Angelika and Binder, Elisabeth B. and Mehta, Divya},
  title     = {Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling},
  series = {Genome Biology},
  volume    = {16},
  journal   = {Genome Biology},
  number    = {266},
  doi       = {10.1186/s13059-015-0828-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149865},
  year      = {2015},
  abstract  = {Background Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. Results We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 \% (110/353) of these CpGs and transcription in 81.7 \% (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. Conclusions Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk.},
  language  = {en}
}
@article{MortonFliesserDittrichetal.2014,
  author    = {Morton, Charles Oliver and Fliesser, Mirjam and Dittrich, Marcus and M{\"u}ller, Tobias and Bauer, Ruth and Kneitz, Susanne and Hope, William and Rogers, Thomas Richard and Einsele, Hermann and L{\"o}ffler, J{\"u}rgen},
  title     = {Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface},
  doi       = {10.1371/journal.pone.0098279},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112893},
  year      = {2014},
  abstract  = {The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.},
  language  = {en}
}