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.
Project description:Intestinal epithelial cells express the lipopolysaccharide (LPS) receptor Toll-like receptor (TLR4) and are responsive to LPS stimulation. Following LPS exposure, epithelial cells, similar to myeloid cells such as macrophages, acquire a state of tolerance. Innate immune tolerance is characterized by a lack of expression of proinflammatory genes in response to repeated stimulation. Tolerant epithelial cells, however, exhibit sustained expression of a distinct set of genes encoding for proteins involved in metabolism and homeostasis. This study comparatively analyzes the gene expression profile 6 hours after LPS stimulation (acute response) versus 6 hours LPS followed by 90 hours incubation in the absence of LPS (tolerant response).
Project description:Intestinal epithelial cells express the lipopolysaccharide (LPS) receptor Toll-like receptor (TLR4) and are responsive to LPS stimulation. Following LPS exposure, epithelial cells, similar to myeloid cells such as macrophages, acquire a state of tolerance. Innate immune tolerance is characterized by a lack of expression of proinflammatory genes in response to repeated stimulation. Tolerant epithelial cells, however, exhibit sustained expression of a distinct set of genes encoding for proteins involved in metabolism and homeostasis. This study comparatively analyzes the gene expression profile 6 hours after LPS stimulation (acute response) versus 6 hours LPS followed by 90 hours incubation in the absence of LPS (tolerant response). We used microarrays to detail the global program of gene expression under unstimulated (control), LPS stimulated (6 hours), and tolerant (96 hours) conditions. Three biological replicates each from naive cells, 6 hour LPS-stimulated cells, and 6 hour LPS-stimulated plus 90 hour LPS-free medium-incubated cells were examined and compared.
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.
Project description:Acute lung inflammation can alter the pulmonary function of susceptible individuals and exacerbate the pathogenesis of chronic inflammatory lung diseases including chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma. Exposure to lipopolysaccharide (LPS) or endotoxin, a constituent of outer cell membrane of gram negative bacteria, induces airway inflammation that is primarily characterized by increased polymorphonuclear neutrophils (PMNs) at early time points. Because LPS is present in variety of occupational and home environments and is an active constituent of cigarette smoke it is a risk factor for increasing prevalence and severity of non-occupational COPD, for adult onset of asthma and for wheezing in children. In airway epithelial cells, LPS stimulation increases mucin gene expression and mucous production. Hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality in chronic inflammatory respiratory lung diseases. In addition, acute bacterial infection contributes to the exacerbation of chronic airway diseases, specifically in advanced COPD and CF subjects, leading to increased healthcare burden and higher mortality. Bcl-2, a prosurvival protein that inhibits cell death plays a key role in normal cellular homeostasis and regulates the integrity of the mitochondrial and endoplasmic reticulum membranes. Gain- and loss-of-function studies showed that Bcl-2 expression sustains hyperplastic epithelial cells, and Bcl-2 expression is elevated in airway epithelial cells of subjects with cystic fibrosis and asthma. The present study investigated which inflammatory mediators induce mucous cell metaplasia and Bcl-2 expression following LPS exposure. Microarray analyses of mRNA from airway epithelial cells captured by laser microdissection from rat lungs snap-frozen at day 0 and 2 post LPS exposure were analyzed. Microarray analysis of mRNA from airway epithelial cells captured by laser microdissection from rat lungs snap-frozen at day 0 and day 2 post LPS exposure was performed to identify inflammatory mediators modulated by LPS exposure.
Project description:Neuroinflammation plays a role in the progression of several neurodegenerative disorders. We used a lipolysaccharide (LPS) model of neuroinflammation to characterize the gene expression changes underlying the inflammatory and behavioral effects of neuroinflammation. A single intracerebroventricular injection of LPS (5 ug) was administered into the lateral ventricle of mice and, 24 hours later, we examined gene expression in the cerebral cortex and hippocampus using microarray technology. Gene Ontology (GO) terms for inflammation and the ribosome were significantly enriched by LPS, whereas GO terms associated with learning and memory had decreased expression. We detected 224 changed transcripts in the cerebral cortex and 170 in the hippocampus. Expression of Egr1 (also known as Zif268) and Arc, two genes associated with learning and memory, was significantly lower in the cortex, but not hippocampus, of LPS-treated animals. Overall, altered expression of these genes may underlie some of the inflammatory and behavioral effects of neuroinflammation.