scholarly journals TMIC-27. GLIOMA CELLS INDUCE ‘EPIGENETIC MEMORY’ IN MICROGLIA AND BLOCK INFLAMMATORY GENE EXPRESSION- IN VITRO AND IN VIVO FINDINGS

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi262-vi262
Author(s):  
Bozena Kaminska ◽  
Marta Maleszewska ◽  
Aleksandra Steranka ◽  
Magdalena Smiech ◽  
Beata Kaza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glioma Cells ◽  
Epigenetic Memory ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

Targeted adenovirus mediated inhibition of NF-κB-dependent inflammatory gene expression in endothelial cells in vitro and in vivo

2013 ◽  
Vol 166 (1) ◽  
pp. 57-65 ◽  
Author(s):  
J.M. Kułdo ◽  
S.A. Ásgeirsdóttir ◽  
P.J. Zwiers ◽  
A.R. Bellu ◽  
M.G. Rots ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene

scholarly journals Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled by S-nitrosylation

2019 ◽  
Vol 317 (5) ◽  
pp. L539-L549 ◽  
Author(s):  
Chang-Jiang Guo ◽  
Elena N. Atochina-Vasserman ◽  
Elena Abramova ◽  
Ley Cody Smith ◽  
Michael F. Beers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Macrophage Phenotype ◽  
Oligomeric State ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Cellular Recruitment

Surfactant protein-D (SP-D) is a regulator of pulmonary innate immunity whose oligomeric state can be altered through S-nitrosylation to regulate its signaling function in macrophages. Here, we examined how nitrosylation of SP-D alters the phenotypic response of macrophages to stimuli both in vivo and in vitro. Bronchoalveolar lavage (BAL) from C57BL6/J and SP-D-overexpressing (SP-D OE) mice was incubated with RAW264.7 cells ± LPS. LPS induces the expression of the inflammatory genes Il1b and Nos2, which is reduced 10-fold by SP-D OE-BAL. S-nitrosylation of the SP-D OE-BAL (SNO-SP-D OE-BAL) abrogated this inhibition. SNO-SP-D OE-BAL alone induced Il1b and Nos2 expression. PCR array analysis of macrophages incubated with SP-D OE-BAL (±LPS) shows increased expression of repair genes, Ccl20, Cxcl1, and Vcam1, that was accentuated by LPS. LPS increases inflammatory gene expression, Il1a, Nos2, Tnf, and Ptgs2, which was accentuated by SNO-SP-D OE-BAL but inhibited by SP-D OE-BAL. The transcription factor NF-κB was identified as a target for SNO-SP-D by IPA, which was confirmed by Trans-AM ELISA in vitro. In vivo, SP-D overexpression increases the burden of infection in a Pneumocystis model while increasing cellular recruitment. Expression of iNOS and the production of NO metabolites were significantly reduced in SP-D OE mice relative to C57BL6/J. Inflammatory gene expression was increased in infected C57BL6/J mice but decreased in SP-D OE. SP-D oligomeric structure was disrupted in C57BL6/J infected mice but unaltered within SP-D OE. Thus SP-D modulates macrophage phenotype and the balance of multimeric to trimeric SP-D is critical to this regulation.

scholarly journals Are Fried Foods Unhealthy? The Dietary Peroxidized Fatty Acid, 13-HPODE, Induces Intestinal Inflammation In Vitro and In Vivo

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 926 ◽  
Author(s):  
Esra’a Keewan ◽  
Chandrakala Aluganti Narasimhulu ◽  
Michael Rohr ◽  
Simran Hamid ◽  
Sampath Parthasarathy
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Inflammatory Disorder ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Gut Mucosa

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by progressive inflammation and the erosion of the gut mucosa. Although the exact cause of IBD is unknown, multiple factors contribute to its complex pathogenesis. Diet is one such factor and a strong correlation exists between the western-style, high fat diets (HFDs) and IBD incidence rates. In this study, we propose that the peroxidized fatty acid components of HFDs could contribute to inflammation of the gut. The inflammatory nature of peroxidized linoleic acid (13-HPODE), was confirmed in vitro by analyzing pro-inflammatory gene expression in Caco-2 cells via RT-PCR and ELISA. Additionally, peroxide induced apoptosis was tested by Annexin-V fluorescent staining, while permeability was tested by FITC-dextran flux and TEER. The 13-HPODE-induced inflammation of intestinal epithelium was evaluated in vivo by analyzing pro-inflammatory cytokines under acute and chronic conditions after feeding 13-HPODE to C57BL/6J mice. Our data show that 13-HPODE significantly induced pro-inflammatory gene expression of TNF-α and MCP-1 in vitro, most notably in differentiated Caco-2 cells. Further, acute and chronic 13-HPODE treatments of mice similarly induced pro-inflammatory cytokine expression in the epithelium of both the proximal and distal small intestines, resident immune cells in Peyer’s patches and peritoneal macrophages. The results of this study not only confirm the pro-inflammatory properties of peroxidized fats on the gut mucosa, but for the first time demonstrate their ability to differentially induce pro-inflammatory gene expression and influence permeability in the intestinal epithelium and mucosal cells. Collectively, our results suggest that the immunogenic properties of HFD’s in the gut may be partly caused by peroxide derivatives, providing potential insight into how these diets contribute to exacerbations of IBD.

scholarly journals LIGHT controls distinct homeostatic and inflammatory gene expression profiles in esophageal fibroblasts via differential HVEM and LTβR-mediated mechanisms

2021 ◽  
Author(s):  
Mario C. Manresa ◽  
Amanda Wu ◽  
Quan M. Nhu ◽  
Austin W. T. Chiang ◽  
Kevin Okamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Primary Fibroblasts ◽  
Inflammatory Phenotype

AbstractFibroblasts mediate tissue remodeling in eosinophilic esophagitis (EoE), a chronic allergen-driven inflammatory pathology. Diverse fibroblast subtypes with homeostasis-regulating or inflammatory profiles have been recognized in various tissues, but which mediators induce these alternate differentiation states remain largely unknown. We recently identified that TNFSF14/LIGHT promotes an inflammatory esophageal fibroblast in vitro. Herein we used esophageal biopsies and primary fibroblasts to investigate the role of the LIGHT receptors, herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTβR), and their downstream activated pathways, in EoE. In addition to promoting inflammatory gene expression, LIGHT down-regulated homeostatic factors including WNTs, BMPs and type 3 semaphorins. In vivo, WNT2B+ fibroblasts were decreased while ICAM-1+ and IL-34+ fibroblasts were expanded in EoE, suggesting that a LIGHT-driven gene signature was imprinted in EoE versus normal esophageal fibroblasts. HVEM and LTβR overexpression and deficiency experiments demonstrated that HVEM regulates a limited subset of LIGHT targets, whereas LTβR controls all transcriptional effects. Pharmacologic blockade of the non-canonical NIK/p100/p52-mediated NF-κB pathway potently silenced LIGHT’s transcriptional effects, with a lesser role found for p65 canonical NF-κB. Collectively, our results show that LIGHT promotes differentiation of esophageal fibroblasts toward an inflammatory phenotype and represses homeostatic gene expression via a LTβR-NIK-p52 NF-κB dominant pathway.

Effect of silencing thymosin beta 4 gene expression on stemness and invasiveness in glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2081-2081
Author(s):  
Ghazaleh Tabatabai ◽  
Shanmugarajan Krishnan ◽  
Ana-Maria Florea ◽  
Karl Frei ◽  
Kathy Hasenbach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Cell Line ◽  
Glioma Cells ◽  
Glioma Stem Cell ◽  
Stem Cell Line ◽  
Self Renewal ◽  
Lentiviral Transduction

2081 Background: Thymosin β4 (TB4) is a pleiotropic actin-sequestering polypeptide that is involved in wound healing and developmental processes. TB4 gene silencing promotes differentiation of neural progenitor cells whereas TB4 overexpression initiates cortical folding of developing brain hemispheres. However, a role of TB4 in malignant gliomas has not yet been investigated. Methods: We first analyzed TB4 expression on tissue microarrays and performed REMBRANDT and TCGA database interrogations. We analyzed TB4 expression in a panel of 8 long-term glioma cell lines and 7 glioma-initiating cell lines. Using lentiviral transduction, we modulated TB4 expression in LNT-229, U87MG and the glioma-initiating cell line GS-2. We studied clonogenic survival, migration, invasion, self-renewal, differentiation capacity of TB4-depleted or TB4-overexpressing glioma cells in vitro and tumorigenicity upon orthotopic implantation in vivo. Finally, we performed an Affymetrix gene chip analysis to unravel the molecular network of TB4 signaling effects. Results: TB4 expression increased with the grade of malignancy in gliomas and correlated with patient survival. In vitro, TB4 gene silencing by lentiviral transduction decreased migration, invasion, growth and self-renewal, and promoted differentiation and the susceptibility to undergo apoptotic cell death upon nutrient depletion in LNT-229, U87MG and the glioma stem-cell line GS2, respectively. In vivo, survival of nude mice bearing tumors derived from TB4-depleted glioma cells was improved and the tumorigenicity of the GS2 glioma stem-cell line was decreased. The gene expression pattern was shifted from the mesenchymal towards the pro-neural gene signature upon TB4 gene silencing. The clustering of differentially regulated genes involved TGF-β and p53 signaling networks. Conclusions: TB4 may be a key regulator of malignancy in glioblastoma and therefore a novel candidate molecular target for anti-glioma therapies.

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