Similar Datasets
Project description:LPS-induced RELA binding, H3K27ac changes and gene expression in pharyngeal epithelial FaDu cells
| PRJNA545639 | ENA
Project description:Gram negative endotoxin Lypopolysaccharide (LPS) leads to a strong innate immune response through TLR4 signalling. This latter pathway activates cannonical NF-kB pathway, including its member RELA. Here, we want to investigate the RELA response in terms of DNA binding as well as epigenetic changes induced by LPS recognition.
2019-06-01 | GSE132018 | GEO
Project description:We report changes in H3K27ac following LPS stimulation in Detroit 562 cells. We were able to identified LPS-increased H3K27ac regions which correlated with RELA binding as well as gene up-regulation. This data set is relevant for airborne bacterial sensing as Detroit 562 cells are nasopharyngeal epithelial cells and LPS is a gram negative bacterial endotoxin.
2018-09-24 | GSE104635 | GEO
Project description:LPS-induced genome-wide RELA binding sites and H3K27ac changes in phraryngeal epithelial cells
| PRJNA545651 | ENA
Project description:Changes in H3K27ac following LPS stimulation in pharyngeal epithelial cells
| PRJNA413376 | ENA
Project description:BackgroundThe epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and mounting an effective immune response via the expression of target genes such as cytokines and chemokines. Gene expression regulation following microbial recognition is partly regulated by chromatin re-organization and has been described in immune cells but data from epithelial cells is not as detailed. Here, we report genome-wide changes of the H3K27ac mark, characteristic of activated enhancers and promoters, after stimulation of nasopharyngeal epithelial cells with the bacterial endotoxin Lipopolysaccharide (LPS).ResultsIn this study, we have identified 626 regions where the H3K27ac mark showed reproducible increase following LPS induction in epithelial cells. This indicated that sensing of LPS led to opening of the chromatin in our system. Moreover, this phenomenon seemed to happen extensively at enhancers regions and we could observe instances of Super-enhancer formation. As expected, LPS-increased H3K27ac regions were found in the vicinity of genes relevant for LPS response and these changes correlated with up-regulation of their expression. In addition, we found the induction of H3K27ac mark to overlap with the binding of one of the NF-kB members and key regulator of the innate immune response, RELA, following LPS sensing. Indeed, inhibiting the NF-kB pathway abolished the deposition of H3K27ac at the TNF locus, a target of RELA, suggesting that these two phenomena are associated.ConclusionsEnhancers' selection and activation following microbial or inflammatory stimuli has been described previously and shown to be mediated via the NF-kB pathway. Here, we demonstrate that this is also likely to occur in the case of LPS-sensing by nasopharyngeal epithelial cells as well. In addition to validating previous findings, we generated a valuable data set relevant to the host immune response to epithelial cell colonizing or infecting pathogens.
| S-EPMC6307289 | biostudies-literature
Project description:Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genome-wide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).
| S-EPMC7468443 | biostudies-literature
Project description:Preeclampsia is a pregnancy complication classified by new onset of elevated blood pressure and proteinuria after 20 weeks of gestation. During preeclampsia, extra villous trophoblasts fail to adequately invade the myometrial spiral arteries, leading to incomplete and impaired vessel transformation and initiating or aggravating preeclampsia. Although NF-κB and proinflammatory cytokines have been reported to be related to trophoblast dysfunction, the underlying mechanism remains unclear. Herein, we demonstrated the miR-138/RELA axis modulating the migratory ability, and invasive ability of HTR-8/SVneo and JEG-3 cells, as well as the inflammatory factor levels in response to LPS stimulation. miR-138 expression was upregulated in preeclampsia placenta and LPS-stimulated HTR-8/SVneo and JEG-3 cell lines. miR-138 overexpression rescued the migratory and invasive ability of HTR-8/SVneo and JEG-3 cells inhibited by LPS stimulation, and decreased LPS-induced TNF-α and IL-6 levels. By binding the 3'-UTR of RELA, miR-138 negatively regulated p65 expression. The silencing of p65 also improved LPS-induced HTR-8/SVneo and JEG-3 cell dysfunction and TNF-α and IL-6 levels. More importantly, p65 overexpression partially reversed the functions of miR-138 overexpression upon both cells, indicating that miR-138 exerted its biological effects through targeting RELA. In conclusion, miR-138 improves LPS-induced inflammation and oxidative stress on trophoblasts through targeting RELA and affecting NF-κB signaling. The miR-138/RELA axis might be involved in preeclampsia pathogenesis, which requires further in vivo and clinical researches.
| S-EPMC8018409 | biostudies-literature
Project description:Gram negative endotoxin Lypopolysaccharide (LPS) leads to a strong innate immune response through TLR4 signalling. This latter pathway activates cannonical NF-kB pathway, including its member RELA. Here, we want to investigate the gene expression response induced by LPS recognition.
2019-06-01 | GSE132019 | GEO
Project description:Adipose tissue inflammation is believed to play a pivotal role in the development obesity-related morbidities such as insulin resistance. However, it is not known how this (low-grade) inflammatory state develops. It has been proposed that the leakage of lipopolysaccharides (LPS), originating from the gut microbiota, through the gut epithelium could drive initiation of inflammation. To get a better understanding of which proteins and intracellular pathways are affected by LPS in adipocytes, we performed SILAC proteomic analysis and identified proteins that were altered in expression. Furthermore, we tested the anti-inflammatory compound resveratrol. A total of 927 proteins were quantified by the SILAC method and of these 57- and 64 were significantly up- and downregulated by LPS, respectively. Bioinformatic analysis (GO analysis) revealed that the upregulated proteins were especially involved in the pathways of respiratory electron transport chain and inflammation. The downregulated proteins were especially involved in protein glycosylation. One of the latter proteins, GALNT2, has previously been described to regulate the expression of liver lipases such as ANGPTL3 and apoC-III affecting lipid metabolism. Furthermore, LPS treatment reduced the protein levels of the insulin sensitizing adipokine, adiponectin, and proteins participating in the final steps of triglyceride- and cholesterol synthesis. Generally, resveratrol opposed the effect induced by LPS and, as such, functioning as an ameliorating factor in disease state. Using an unbiased proteomic approach, we present novel insight of how the proteome is altered in adipocytes in response to LPS as seen in obesity. We suggest that LPS partly exerts its detrimental effects by altering glycosylation processes of the cell, which is starting to emerge as important posttranscriptional regulators of protein expression. Furthermore, resveratrol could be a prime candidate in ameliorating dysfunctioning adipose tissue induced by inflammatory stimulation.
| S-EPMC4954707 | biostudies-literature