Ncf1 provides a reactive oxygen species-independent negative feedback regulation of TLR9-induced IL-12p70 in murine dendritic cells.

Permanent exposure to pathogens requires decisions toward tolerance or immunity as a prime task of dendritic cells. The molecular mechanisms preventing uncontrolled immune responses are not completely clear. We investigated the regulatory function of Ncf1, an organizing protein of NADPH oxidase, in the signaling cascade of Toll-like receptors.

Computer-aided analysis of cell interactions under dynamic flow conditions.

Experimentally, initial steps of leucocyte extravasation, including tethering and rolling, are analysed in endothelial cell flow chambers. Given the complexity and speed of endothelial-immune cell interaction, computer-aided advances of this analysis are highly desirable. Herein, we compared two established methods, hand counting and tracking software, with novel analysis software using defined movies recorded at standard conditions of endothelial-leucocyte interactions.

TLR-ligand stimulated interleukin-23 subunit expression and assembly is regulated differentially in murine plasmacytoid and myeloid dendritic cells.

Interleukin-23 (IL-23) is a heterodimeric cytokine composed of the p40 and p19 subunits, the first of which is also part of the IL-12 heterodimer. IL-23 induces a unique T helper cell subset to produce IL-17, which plays a critical and IL-12/IFN-gamma-independent role in autoimmunity. Plasmacytoid dendritic cells (pDC), as opposed to myeloid DC (mDC) and the closely related epidermal Langerhans cells (LC), exhibit a specific and broad range of pro-inflammatory cytokine secretion, with type I interferons representing a typical difference to classical mDC and LC.

Histone deacetylase 3, a class I histone deacetylase, suppresses MAPK11-mediated activating transcription factor-2 activation and represses TNF gene expression.

During inflammatory events, the induction of immediate-early genes, such as TNF-alpha, is regulated by signaling cascades including the JAK/STAT, NF-kappaB, and the p38 MAPK pathways, which result in phosphorylation-dependent activation of transcription factors. We observed the direct interaction of histone deacetylase (HDAC) 3, a class I histone deacetylase, with MAPK11 (p38 beta isoform) by West-Western-based screening analysis, pull-down assay, and two-hybrid system analysis. Results further indicated that HDAC3 decreases the MAPK11 phosphorylation state and inhibits the activity of the MAPK11-dependent transcription factor, activating transcription factor-2 (ATF-2).

Chromosomal organization and localization of the human histone deacetylase 9 gene (HDAC9).

Epigenetically mediated modulation of gene promoter function through histone acetylation modifying enzymes, which regulate the acetylation state of histone proteins and other promoter-bound transcription factors, is increasingly appreciated as a key component in the regulation of reversible gene expression. While histone acetyltransferases (HATs), which are frequently part of multisubunit coactivator complexes, lead to the relaxation of chromatin structure and transcriptional activation, histone deacetylases (HDACs) tend to associate with multisubunit corepressor complexes, which result in chromatin condensation and transcriptional repression of specific target genes. We have isolated and characterized the human HDAC9 genomic sequence, which spans a region of 458 kb and which has one single chromosomal locus.