scholarly journals Long noncoding RNA GSEC promotes neutrophil inflammatory activation by supporting PFKFB3-involved glycolytic metabolism in sepsis

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Dadong Liu ◽  
Wen Sun ◽  
Danying Zhang ◽  
Zongying Yu ◽  
Weiting Qin ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Inflammatory Cytokine ◽  
Process Analysis ◽  
Expression Patterns ◽  
Cytokine Expression ◽  
Neutrophil Activation ◽  
Metabolic Reprogramming ◽  
Glycolytic Metabolism ◽  
Inflammatory Activation

AbstractMetabolic reprogramming is a hallmark of neutrophil activation in sepsis. LncRNAs play important roles in manipulating cell metabolism; however, their specific involvement in neutrophil activation in sepsis remains unclear. Here we found that 11 lncRNAs and 105 mRNAs were differentially expressed in three transcriptome datasets (GSE13904, GSE28750, and GSE64457) of gene expression in blood leukocytes and neutrophils of septic patients and healthy volunteers. After Gene Ontology biological process analysis and lncRNA–mRNA pathway network construction, we noticed that GSEC lncRNA and PFKFB3 were co-expressed and associated with enhanced glycolytic metabolism. Our clinical observations confirmed the expression patterns of GSEC lncRNA and PFKFB3 genes in neutrophils in septic patients. Performing in vitro experiments, we found that the expression of GSEC lncRNA and PFKFB3 was increased when neutrophils were treated with inflammatory stimuli. Knockdown and overexpression experiments showed that GSEC lncRNA was essential for mediating PFKFB3 mRNA expression and stability in neutrophil-like dHL-60 cells. In addition, we found that GSEC lncRNA-induced PFKFB3 expression was essential for mediating dHL-60 cell inflammatory cytokine expression. Performing mechanistic experiments, we found that glycolytic metabolism with PFKFB3 involvement supported inflammatory cytokine expression. In summary, our study uncovers a mechanism by which GSEC lncRNA promotes neutrophil inflammatory activation in sepsis by supporting glycolytic metabolism with PFKFB3.

scholarly journals SOCS1/SOCS3 Immune Axis Modulates Synthetic Perturbations in IL6 Biological Circuit for Dynamical Cellular Response

2020 ◽  
Author(s):  
Bhavnita Soni ◽  
Shailza Singh
Keyword(s):  
Signaling Pathway ◽  
Cellular Response ◽  
Inflammatory Cytokine ◽  
Cytokine Expression ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Macrophage Phenotype ◽  
Regulatory Circuit ◽  
Stat Pathway

AbstractMacrophage phenotype plays a crucial role in the pathogenesis of Leishmanial infection. Pro-inflammatory cytokines are the key regulators that eliminate the infection induced by Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Suppressor of cytokine signaling (SOCS) is a well-known negative feedback regulator of JAK/STAT pathway. However, change in expression levels of SOCS in correlation with the establishment of infection is not well understood. Mathematical modeling of IL6 signaling pathway have helped identified the role of SOCS1 in establishment of infection. Furthermore, the ratio of SOCS1 and SOCS3 has been quantified both in silico as well as in vitro, indicating an immune axis which governs the macrophage phenotype during L. major infection. The ability of SOCS1 protein to inhibit the JAK/STAT1 signaling pathway and thereby decreasing pro-inflammatory cytokine expression makes it a strong candidate for therapeutic intervention. Using synthetic biology approaches, peptide based immuno-regulatory circuit have been designed to target the activity of SOCS1 which can restore pro-inflammatory cytokine expression during infection.

1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro

2017 ◽  
Vol 27 (7) ◽  
pp. 1530-1537 ◽  
Author(s):  
Natalija Knežević Teofilović ◽  
Mahjoub Bihi ◽  
Marijana Radić Stojković ◽  
Lidija M. Tumir ◽  
Katja Ester ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Expression

scholarly journals p53 mutations exhibit sex specific gain-of-function activity in gliomagenesis

2021 ◽  
Author(s):  
Nathan C Rockwell ◽  
Wei Yang ◽  
Nicole Warrington ◽  
Malachi Griffith ◽  
Obi L Griffith ◽  
...  
Keyword(s):  
Dna Binding ◽  
Expression Patterns ◽  
Metabolic Reprogramming ◽  
Mutant P53 ◽  
Small Male ◽  
Missense Mutations ◽  
P53 Mutations ◽  
Gain Of Function ◽  
Primary Mouse

The tumor suppressor TP53 is the most frequently mutated gene in cancer. Most TP53 mutations are missense mutations in the DNA-binding domain, which in addition to loss of canonical p53 activity, frequently confer gain-of-function (GOF) aberrant transcriptional activity through mutant p53 localization to non-canonical genes. GOF phenotypes differ by mutation and cell identity and are reported to include increased proliferation, migration, metabolic reprogramming, and therapy resistance. We found that several recurring p53 mutations exhibit a sex-bias in patients with glioblastoma (GBM). In vitro and in vivo analysis of three mutations, p53R172H, p53Y202C, and p53Y217C revealed sex differences in each mutation′s ability to transform primary mouse astrocytes. p53R172H exhibited a far greater ability to transform female astrocytes than males, p53Y202C transformed both male and female astrocytes with a small male bias, and p53Y217C only exhibited GOF transformation effects in male astrocytes. These phenotypic differences reflect an interaction between sex and GOF mutation to drive unique gene expression patterns in cancer pathways. We found that mutant p53 exhibits sex and mutation specific aberrant genomic localization to the transcriptional start sites of upregulated genes, whose promoter regions were enriched for different sets of transcription factor DNA-binding motifs. Together, our data establish a novel paradigm for sex specific mutant p53 GOF activity in GBM with implications for all cancer.

scholarly journals Sophorolipid treatment decreases inflammatory cytokine expression in an in vitro model of experimental sepsis

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Cathy M Mueller ◽  
Yin‐yao Lin ◽  
Domenico Viterbo ◽  
Joelle Pierre ◽  
Shirley A Murray ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
In Vitro Model ◽  
Cytokine Expression ◽  
Experimental Sepsis ◽  
Vitro Model

Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression in vivo and in vitro

2018 ◽  
Vol 56 ◽  
pp. 135-142 ◽  
Author(s):  
Jeong-Min Lim ◽  
Bina Lee ◽  
Ju-Hee Min ◽  
Eun-Young Kim ◽  
Jae-Hyun Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Inflammatory Cytokine ◽  
Cytokine Expression

scholarly journals Lactate Metabolism Regulates Tumour Growth and Progression in Glioblastoma

2021 ◽  
Author(s):  
Lucia Longhitano ◽  
Nunzio Vicario ◽  
Daniele Tibullo ◽  
Cesarina Giallongo ◽  
Giuseppe Broggi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Metabolic Reprogramming ◽  
In Vivo Model ◽  
Glycolytic Metabolism ◽  
Mesenchymal Transition ◽  
Signalling Molecule ◽  
Extracellular Lactate ◽  
Human Gbm

Abstract Background. Tumor microenvironment (TME) plays a pivotal role in establishing malignancy and it is associated with high glycolytic metabolism and increased lactate production accumulating in TME through monocarboxylate transporters (MCTs). Several lines of evidence suggest that lactate also serves as a signalling molecule through its receptor HCAR1thus functioning as a paracrine and autocrine signalling molecule in TME. The aim of the present study was to investigate the role of lactate in glioblastoma (GBM) progression and metabolic reprogramming in an in vitro and in vivo model.Methods. Cell proliferation, migration and clonogenicity assay were performed in vitro on three different human GBM cell lines. Protein expression of MCT1, MCT4 and pharmacological lactate receptor (GPR81) were evaluated both in vitro and in a zebrafish GBM in vivo model. These results were further validated in patient-derived GBM biopsies.Results. Our results showed that lactate significantly increased cell proliferation, migration and colony formation capacity of GBM cells, both in vitro and in vivo. We also showed that lactate increased MCT1 and HCAR1 expression. Moreover, lactate modulated epithelial-mesenchymal transition protein markers E-Cadherin and β-Catenin. Interestingly, lactate induced mitochondrial mass and OXPHOS gene suggesting an improved mitochondrial fitness. Similar effects were observed after treatment with 3,5-Dihydroxybenzoic acid, a known agonist of GPR81. Consistently, GBM zebrafish model exhibited an altered metabolism and increased expression of MCT1 and HCAR1 leading to high levels of extracellular lactate and thus supporting tumor cell proliferation. Our data from human GBM biopsies also showed that in high proliferative GBM biopsies, Ki67 positive cells expressed significantly higher levels of MCT1 compared to low proliferative GBM cells.Conclusions. Our data suggest that lactate favours proliferation of neighbourhood cells by cooperating with their glycolytic metabolism, sensing and removing extracellular lactate. In particular, lactate and its transporter and receptor play a major role in GBM proliferation and migration thus representing a potential target to develop new strategies to counteract tumor progression and recurrencies.

Sign in / Sign up

Export Citation Format

Share Document