P53 amplifies Toll-like receptor 5 response in MCF-7 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72359 | GEO | 2015/08/26
SECONDARY ACCESSION(S): PRJNA293871
REPOSITORIES: GEO
Similar Datasets
Project description:Using gene expression profiling we characterize the global effect of p53 on the TLR5-mediated transcription in MCF7 cells. We found that combined activation of p53 and TLR5 pathways synergistically increases expression of over 200 genes, mostly associated with immunity and inflammation. The synergy was observed in several human cancer cells and primary lymphocytes. Oncotarget. 2015 Jul 10;6(19):16963-80, PMID 26220208 10 experimental conditions, each in triplicate, several samples were hybridized twice at two separate ocasions as indicated in 'description' field. 29 samples total and 35 arrays total.
2015-08-26 | E-GEOD-72359 | biostudies-arrayexpress
Project description:Flagellins from commensal bacteria can be weak Toll-like receptor (TLR)5 agonists despite high affinity binding to TLR5, ligands we termed “silent flagellins”. To determine if silent flagellins are detectable in the human gut, endogenous flagellins produced by the microbiota were isolated from stool obtained from a healthy adult female donor. TLR5 was used as bait to enrich for silent flagellins and TLR5-bound flagellins were identified by searching peptides against a custom flagellin database built from metagenome sequences.
2022-10-12 | PXD033249 | Pride
Project description:Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation. IPF results from maladaptive responses to lung epithelial injury, but the underlying mechanisms remain unclear. Here, we show that deficiency in the innate immune receptor, toll-like receptor 5 (TLR5), is associated with IPF in humans and with increased susceptibility to experimental fibrosis in mice, while activation of lung epithelial TLR5 through a synthetic flagellin analog protects from experimental fibrosis. Mechanistically, epithelial TLR5 activation induces antimicrobial gene expression and ameliorates dysbiosis after lung injury. In contrast, TLR5 deficiency in mice and IPF patients is associated with lung dysbiosis. Elimination of the microbiome in mice through antibiotics abolishes the protective effect of TLR5 and reconstitution of the microbiome rescues the observed phenotype. In aggregate, TLR5 deficiency is associated with IPF and dysbiosis in humans and in the murine model of pulmonary fibrosis. Furthermore, TLR5 protects against pulmonary fibrosis in mice, and this protection is mediated by effects on the microbiome.
2026-04-03 | GSE314583 | GEO
Project description:TLR5 is a pathogen recognition receptor against flagellin that is expressed in various epithelial and immune cells. Mice pretreated with TLR5-agonist are protected against bleomycin-induced pulmonary fibrosis. However, the mechanisms by which TLR5-agonism protects against pulmonary fibrosis remains to be determined. Here, we found innate host defense gene sets to be selectively elevated in sorted type 2 alveolar epithelial.
2026-04-03 | GSE314582 | GEO
Project description:Entolimod, a pharmacological derivative of the natural Toll-like receptor 5 (TLR5) agonist flagellin, has strong therapeutic potential for several indications including radioprotection and cancer immunotherapy. However, in Phase 1 studies, entolimod induced a rapid neutralizing immune response, presumably due to flagellin-reactive immune memory derived from life-long exposure of adult humans to flagellated enterobacteria. Since applications requiring repeated dosing could be precluded by entolimod’s neutralizing antigenicity and immunogenicity, we used structure-guided reengineering to develop a new, substantially deimmunized entolimod variant, GP532. We used RNAseq-based analysis of global gene expression profiles in C57BL/6 mice following systemic administration of entolimod vs GP532 to evaluate the biocomparability of the two drugs. In this experiment, we used wild type (WT) and TLR5-/- mice (on the same genetic background) to address the TLR5-dependence/specificity of responses and focused on the liver since it was previously defined as the major organ responsive to TLR5 systemic administration in mice . Analysis of livers collected 30 minutes after injection of entolimod or GP532 was aimed at assessing direct primary TLR5 responses, while a 24-hour time point was included (for wild type mice) to define long-term overall (direct and indirect) effects of TLR5 activation. Overall, our RNAseq-based analysis of the effects of entolimod and GP532 on transcription confirmed our expectations of their mechanism of action and overall biocomparability. These results establish GP532 as a highly optimized TLR5 agonist suitable for multi-dose therapeutic regimens and for patients with high titers of preexisting flagellin-neutralizing antibodies.
2020-12-24 | GSE163748 | GEO
Project description:The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. Based on the knowledge that smokers are more susceptible to pulmonary infection and the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters the expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th-12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most strikingly changed gene is TLR5, which down-regulated in healthy smokers (1.4-fold decrease, p<10-13) and in smokers with COPD (1.6-fold, p<10-14). TaqMan RT-PCR confirmed these observations. Bronchial biopsies immunofluorescence showed that TLR5 protein was expressed mainly on the apical side of the human airway epithelium and decreased in healthy smokers and smokers with COPD. In vitro studies showed that the level of TLR5 downstream genes, IL-6 and IL-8 were highly induced in TLR5 high-expressing cells compared to TLR5 low-expressing cells after flagellin exposure. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 likely contributes to smoking-related susceptibility to airway infection. The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense. Microarrays were used to survey the TLR family gene expression in small airway (10th-12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most strikingly changed gene is TLR5, which down-regulated in healthy smokers (1.4-fold decrease, p<10-13) and in smokers with COPD (1.6-fold, p<10-14). In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 likely contributes to smoking-related susceptibility to airway infection. *** Processed data not provided for all gene expression records. ***
2012-10-03 | E-GEOD-30063 | biostudies-arrayexpress
Project description:The toll-like receptors (TLRs) are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. Based on the knowledge that smokers are more susceptible to pulmonary infection and the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters the expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th-12th order) epithelium from healthy nonsmokers (n=60), healthy smokers (n=73) and smokers with COPD (n=36). Using the criteria of detection call of present in ≥50%, 6 of 10 TLRs (1, 2, 3, 4, 5 and 8) were expressed. Compared to nonsmokers, the most strikingly changed gene is TLR5, which down-regulated in healthy smokers (1.4-fold decrease, p<10-13) and in smokers with COPD (1.6-fold, p<10-14). TaqMan RT-PCR confirmed these observations. Bronchial biopsies immunofluorescence showed that TLR5 protein was expressed mainly on the apical side of the human airway epithelium and decreased in healthy smokers and smokers with COPD. In vitro studies showed that the level of TLR5 downstream genes, IL-6 and IL-8 were highly induced in TLR5 high-expressing cells compared to TLR5 low-expressing cells after flagellin exposure. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced down-regulation of TLR5 likely contributes to smoking-related susceptibility to airway infection.
2012-10-03 | GSE30063 | GEO
Project description:Acute radiation syndrome (ARS) is a major cause of lethality following radiation disasters. A TLR5 agonist, entolimod, is among the most powerful experimental radiation countermeasures and shows efficacy in rodents and non-human primates as a prophylactic (radioprotection) and treatment (radiomitigation) modality. While the prophylactic activity of entolimod has been connected to suppression of radiation-induced apoptosis, the mechanism by which entolimod functions as a radiomitigator remains poorly understood. Here, we demonstrate that, in contrast to radioprotection, neutrophils are essential for the radiomitigative activity of entolimod. We found that neutrophils express functional TLR5 and stimulation by entolimod is a key component to the mechanism of radiomitigation. Given that the underlying effects of TLR5 agonists have been associated with NF-kB-dependent transcriptional events, we hypothesized that changes in the transcriptional profile of neutrophils post-entolimod treatment mitigates radiation damage. However, RNA sequencing data analysis showed that ex vivo stimulation of neutrophils with entolimod for 30 minutes caused changes in transcriptional profiles that were substantially weaker – both in the number of responsive genes and scale of changes – as compared with that of liver cells following in vivo entolimod treatment. These observations suggest that mitigation of radiation damage by entolimod-stimulated neutrophils involves a transcriptional-independent mechanism.
2021-09-29 | GSE179808 | GEO
Project description:We reprocessed RNA-Seq data for 1,558 samples across 8 tissue sites from the GTEx project. We follow the exact pipeline performed by Rahman et al. Bioifnormatics 2015 (PMID: 26209429)
2017-07-12 | GSE86354 | GEO
Project description:Cancer cachexia is highly prevalent in gastric cancer patients and is characterized by decreased food consumption and body weight. We previously created a rat model of cancer cachexia using MKN45cl85 and 85As2 cells derived from human gastric cancer. The 85As2 cells induced cachexia more potently than MKN45cl85 cells did. To clarify the mechanism underlying the difference in the cachexia-inducing ability of these cells, we conducted a DNA microarray analysis, with a focus on cell proliferation and the production of leukemia inhibitory factor (LIF), a cachexia-inducing factor. The plasma human LIF levels of 85As2-induced cachexic rats increased in parallel with the worsening of symptoms whereas the plasma levels of MKNcl85 were low. 85As2 cells displayed more genetic changes than MKN45cl85 cells did, which were related to Toll-like receptor (TLR) 4//5 signaling. Stimulation of both the cells with TLR4 (lipopolysaccharide) or TLR5 (flagellin) agonists did not affect proliferation. However, in 82As2 cells, LIF production was significantly increased by stimulation with TLR5, which was suppressed by an inhibitor of interleukin-1 receptor-associated kinase-1/4, which are important factors in the TLR5 signaling pathway. In conclusion, it is possible that the increase in LIF production through the activation of the TLR5 signaling pathway contributes to the cachexia-inducing ability of 85As2 cells.
2018-11-14 | GSE113110 | GEO