Transcriptomic changes in macrophages induced by damage-associated molecular patterns (DAMPs)
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ABSTRACT:
PROVIDER: PRJNA632501 | ENA |
REPOSITORIES: ENA
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Project description:Dead cell-derived molecules, typically called as damage-accociated molecular patterns (DAMPs), have been shown to evoke inflammatory responses. Accordingly, it becomes increasingly clear that DAMPs play important role in pathogenesis of multiple diseases including inflammatory diseases and cancer. To get a comprihensive view of DAMP-mediated inflammatory responses, we perfomed microarray analysis on murine macrophages treated by dead cell-derived molecules.
2021-05-21 | GSE150465 | GEO
Project description:The molecular hallmark of immunogenic cell death (ICD) features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Herein, measuring DAMPs from gemcitabine-induced dying cancer cells, via mass spectrometry (MS) proteomic profiling.
2020-10-29 | MSV000086386 | MassIVE
Project description:The molecular hallmark of immunogenic cell death (ICD) features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Herein, measuring DAMPs from gemcitabine-induced dying cancer cells, via mass spectrometry (MS) proteomic profiling.
2020-11-04 | MSV000086407 | MassIVE
Project description:Dying cells release Damage-Associated Molecular Patterns (DAMPs) that can initiate and perpetuate sterile inflammatory responses. However, the effect of DAMPs on macrophages biology remains unclear. We therefore studied the effect of DAMPs on primary peritoneal macrophages (PPM) in vitro. We first performed unbiased transcriptomic profiling with RNA-seq of PPMs cultured for up to 72 hours in the presence and absence of: 1) liposaccharide (LPS), which is known to provoke an “M1” phenotype, 2) IL-4, which is known to provoke an “M2” phenotype, or 3) cytosolic extracts (CEs) from necrotic H9C2 cells to mimic the release of cardiomyocyte DAMPs. We found that the transcriptional profile of PPMs stimulated with CEs resembled the transcriptional profile of PPMs stimulated with LPS.
2019-08-21 | GSE107776 | GEO
Project description:To explore the differently expressed genes in BMDM after the treatment with S1P or DAMPs (Damage associated molecular patterns). BMDM cells were incubated with apoptotic cell culture medium (ACM) or S1P (500nM) for 24 hours before harvest for RNA extraction. ACM generated from palmitic acid treated AML12 cells was used as DAMPs. We also want to see whether these genes regulated by S1P or DAMPs are Trem2 dependent or independent.
2022-12-06 | GSE193577 | GEO
Project description:Purpose: The optic nerve head (ONH) is well known to be the initial site of glaucomatous damage. However, the molecular mechanisms initiating this pathology are not fully understood. To further understand the initiating factors in glaucomatous damage we utilized a novel mouse model of glaucoma, B6.EDA+/+ mice, that constitutively express FN containing the EDA domain (FN+EDA). FN+EDA is a known damage associated molecular pattern (DAMP) that activates toll-like receptor 4 (TLR4) and elicits a fibro-inflammatory response. Results: B6.EDA+/+ mice exhibit significantly higher IOP, loss of RGCs, thinning of the RNFL, and progressive levels of ON damage at 12 months and 22 months of age compared to C57BL/6J controls. Protein expression of DAMPs FN+EDA and biglycan were significantly increased in B6.EDA+/+ mice compared to C57BL/6J controls. GSEA analysis identified significantly up- and down-regulated gene groupings at both 12 months and 22 months of age, and IHC staining demonstrated significant increases of IFNα, IFNβ, and pSTAT1 expression in B6.EDA+/+ mice compared to C57BL/6J controls. Conclusions: Our study characterizes glaucomatous changes to the retina, ON, and ONH over the course of two years and identifies novel molecular pathways associated with these pathophysiological changes. These data indicate time specific DAMP production and immune system signaling in a novel mouse model of glaucoma.
2024-10-16 | GSE270934 | GEO
Project description:Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients’ plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients’ plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and worsening of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.
2023-09-18 | GSE236194 | GEO
Project description:Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients’ plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients’ plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and worsening of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.
2023-09-18 | GSE236193 | GEO
Project description:Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients’ plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients’ plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and worsening of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.
2023-09-18 | GSE236192 | GEO
Project description:DAMPs drive Fibroinflammatory Changes in the glaucomatous ONH
| PRJNA1129064 | ENA