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NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses
The objective of this study was to explore the role of NOD2 and TLR2 in cross-presentation in human dendritic cells undertaking an unbiased screen. We have used a quantitative phosphoproteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by a computational analysis to identify the proteins as differentially abundant in response to NOD2 and TLR2 sensing. Validation of the phosphoproteomic analysis was performed by the detection of proteins in phosphoenriched lysates and detected by western blot. Techniques for the modulation of gene expression (shRNA and siRNA) were used to confirm the resu...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.
Abstract Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPK-inhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity...
Source: Autophagy - March 26, 2019 Category: Cytology Authors: Fernandez-Mosquera L, Yambire KF, Couto R, Pereyra L, Pabis K, Ponsford AH, Diogo CV, Stagi M, Milosevic I, Raimundo N Tags: Autophagy Source Type: research

Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells
Conclusions: We propose that the inhibition of chromatin assembly represents a novel mechanism of cell transformation induced by the environmental and occupational chemical carcinogen FA. https://doi.org/10.1289/EHP1275 Received: 25 October 2016 Revised: 19 May 2017 Accepted: 23 May 2017 Published: 21 September 2017 Address correspondence to C. Jin, Dept. of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd., Tuxedo Park, NY 10987 USA. Telephone: (845) 731-3602. Email: Chunyuan.jin@nyumc.org *Current affiliation: Medical School of Nanjing University, Nanjing, China. †Current affiliatio...
Source: EHP Research - September 21, 2017 Category: Environmental Health Authors: Daniil Lyalko Tags: Research Source Type: research