Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

ABSTRACT: The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-?, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

SUBMITTER: Lang S

PROVIDER: S-EPMC5207674 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

Lang Shan S Li Libing L Wang Xuning X Sun Junping J Xue Xinying X Xiao Yongjiu Y Zhang Mingyue M Ao Ting T Wang Jianxin J

PloS one 20170103 1

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting ...[more]

PMID: 28046003

Similar Datasets

An IP-10 (CXCL10)-derived peptide inhibits angiogenesis.

Project description:Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the ?-helical domain residues 77-98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis.

| S-EPMC3397949 | biostudies-literature

Macrophages induce differentiation of plasma cells through CXCL10/IP-10.

Project description:In tonsils, CD138(+) plasma cells (PCs) are surrounded by CD163(+) resident macrophages (Ms). We show here that human Ms (isolated from tonsils or generated from monocytes in vitro) drive activated B cells to differentiate into CD138(+)CD38(++) PCs through secreted CXCL10/IP-10 and VCAM-1 contact. IP-10 production by Ms is induced by B cell-derived IL-6 and depends on STAT3 phosphorylation. Furthermore, IP-10 amplifies the production of IL-6 by B cells, which sustains the STAT3 signals that lead to PC differentiation. IP-10-deficient mice challenged with NP-Ficoll show a decreased frequency of NP-specific PCs and lower titers of antibodies. Thus, our results reveal a novel dialog between Ms and B cells, in which IP-10 acts as a PC differentiation factor.

| S-EPMC3457728 | biostudies-literature

Microarray expression profile of circular RNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome

Project description:Acute respiratory distress syndrome (ARDS) remains a common and devastating syndrome. CircRNAs are crucial in a variety of diseases and can provide new potential diagnostic and therapeutic targets for disease. The development of circular RNA (circRNA) microarray has facilitated the study of the role of circRNAs in regulating gene expression. This research was designed to explore the expression profile of circRNAs in lung tissues from rats with lipopolysaccharide-induced ARDS. Our findings indicate that the expression profiles of circRNAs has changed in ARDS as compared with normal rat lung tissue, and may provide novel insight into the molecular mechanism underlying the disease and potential novel diagnostic or therapeutic targets for ARDS.

2017-08-12 | GSE102523 | GEO

IP-10/CXCL10 attracts regulatory T cells: Implication for pancreatic cancer.

Project description:Pancreatic stellate cells (PSCs) are key components of pancreatic ductal adenocarcinoma (PDAC). We recently demonstrated that IP-10/CXCL10 is highly expressed by PSCs in the presence of pancreatic cancer cells (PCCs) and its expression correlates with infiltration by regulatory T cells (Tregs) and poor survival. Thus, stromal cells in pancreatic cancer can promote immunosuppression and tumor progression, through the expression of IP-10.

| S-EPMC4570127 | biostudies-literature

Injury-induced MRP8/MRP14 stimulates IP-10/CXCL10 in monocytes/macrophages.

Project description:Trauma/hemorrhagic shock is associated with morbidity and mortality due to dysregulated inflammation, which is driven in part by monocytes/macrophages stimulated by injury-induced release of damage-associated molecular pattern (DAMP) molecules. MRP8/MRP14 is an endogenous DAMP involved in various inflammatory diseases, though its mechanism of action is unclear. Circulating MRP8/MRP14 levels in human blunt trauma nonsurvivors were significantly lower than those of survivors (P < 0.001). Human monocytic THP-1 cells stimulated with MRP8/MRP14 expressed the chemokine IFN-γ inducible protein 10 (IP-10)/CXCL10. Circulating IP-10 levels in human blunt trauma patients were correlated positively with MRP8/MRP14 levels (r = 0.396, P < 0.001), and were significantly lower in trauma nonsurvivors than in survivors (P < 0.001). We therefore sought to determine the mechanisms by which MRP8/MRP14 stimulates IP-10 in monocytes/macrophages, and found that induction of IP-10 by MRP8/MRP14 required Toll-like receptor 4 and TRIF but not MyD88. Full induction of IP-10 by MRP8/MRP14 required synergy between the transcription factors NF-κB and IFN regulatory factor 3 (IRF3). The receptor for IP-10 is CXCR3, and MRP8/MRP14-induced chemotaxis of CXCR3(+) cells was dependent on the production of IP-10 in monocytes/macrophages. Furthermore, in vivo study with a mouse trauma/hemorrhagic shock model showed that administration of neutralizing antibody against MRP8 prevented activation of NF-κB and IRF3 as well as IP-10 production. Thus, the current study identified a novel signaling mechanism that controls IP-10 expression in monocytes/macrophages by MRP8/MRP14, which may play an important role in injury-induced inflammation.

| S-EPMC4285539 | biostudies-literature

BRD4 targeting nanotherapy prevents lipopolysaccharide induced acute respiratory distress syndrome.

Project description:Acute respiratory distress syndrome (ARDS) is a life threatening respiratory disease associated with pulmonary edema, alveolar dysfunction, hypoxia, and inflammatory cell accumulation. The most contagious form of COVID-19 associated with ARDS caused by SARS-CoV-2. SARS-CoV-2 majorly produces the cytokine storm and severe lung inflammation and ultimately leads to respiratory failure. ARDS is a complex disease and there is no proper therapeutics for effective therapy. Still, there is a huge scope to identify novel targets to combat respiratory illness. In the current study, we have identified the epigenetic regulating protein BRD4 and developed siRNA based nanomedicine to treat the ARDS. The liposomes were prepared by thin-film hydration method, where BRD4 siRNA complexed with cationic lipid and exhibited 96.24 ± 18.01 nm size and stable even in the presence of RNase. BRD4 siRNA lipoplexes (BRD4-siRNA-LP) inhibited inflammatory cells in lungs and suppressed the lipopolysaccharide (LPS) induced the neutrophil infiltration and mast cell accumulation. Also, BRD4 siRNA based nanomedicine significantly reduced the LPS induced cytokine storm followed by inflammatory signaling pathways. Interestingly, BRD4-siRNA-LP suppressed the LPS-induced p65 and STAT3 nuclear translocation and ameliorated the lung inflammation. Thus, BRD4-siRNA-LP could be a plausible therapeutic option for treating ARDS and might be useful for combating the COVID-19 associated respiratory illness.

| S-EPMC7997899 | biostudies-literature

Total alveolar lavage with oxygen fine bubble dispersion directly improves lipopolysaccharide-induced acute respiratory distress syndrome of rats.

Project description:Severe respiratory disorder induced by pulmonary inflammation is one of the causes of acute respiratory distress syndrome, which still has high mortality. It is crucial to remove causative substances and inflammatory mediators early in order to inhibit the progression of pulmonary inflammation. Total alveolar lavage (TAL) may avert the inflammatory response by eliminating causative substances in certain inflammatory lung diseases. We developed an efficient TAL system and examined the efficacy of short-term TAL treatment performed for acute lung injury models of rats. In the first experiment with a severe lung injury model, 15 rats were divided into 3 groups: sham group, mechanical gas ventilation (MGV) treatment group, and TAL treatment group. The treatments were conducted for 5 min, 20 min after the provocation of inflammation. Two days after treatment, the TAL and MGV treatment groups exhibited significant differences in blood oxygen levels, mean arterial pressure, weight-loss ratio, and inflammatory cytokine levels in the lungs. In contrast, almost no differences were observed between the TAL treatment and sham groups. In the second experiment with a lethal lung injury model, the TAL treatment dramatically improved the survival rate of the rats compared to the MGV treatment groups (p = 0.0079). Histopathological analysis confirmed pronounced differences in neutrophil accumulation and thickening of the interstitial membrane between the TAL and MGV treatment groups in both experiments. These results indicate that as little as 5 min of TAL treatment can protect rats from acute lung injury by removing causative substances from the lungs.

| S-EPMC7538589 | biostudies-literature

Microarray expression profile of circular RNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome.

Project description:The data presented in this article are related to the research article entitled "The expression profiles of circRNAs in lung tissues from rats with lipopolysaccharide-induced acute respiratory distress syndrome (ARDS): A microarray study." (Wan et al., 2017) [1]. ARDS remains a common and devastating syndrome. The development of circRNA microarray has facilitated the study of the role of circRNAs in regulating gene expression in ARDS. This research was designed to explore the expression profile of circRNAs in lung tissues from rats with lipopolysaccharide-induced ARDS. The field dataset is made publicly available to enable critical or extended analyzes.

| S-EPMC5655385 | biostudies-literature

PDGFR-alpha inhibits melanoma growth via CXCL10/IP-10: a multi-omics approach.

Project description:Melanoma is the most aggressive skin-cancer, showing high mortality at advanced stages. Platelet Derived Growth Factor Receptor-alpha (PDGFR-alpha) potently inhibits melanoma- and endothelium-proliferation and its expression is significantly reduced in melanoma-biopsies, suggesting that melanoma progression eliminates cells expressing PDGFR-alpha. In the present study transient overexpression of PDGFR-alpha in endothelial (HUVEC) and melanoma (SKMel-28, A375, Preyer) human-cells shows strong anti-proliferative effects, with profound transcriptome and miRNome deregulation. PDGFR-alpha overexpression strongly affects expression of 82 genes in HUVEC (41 up-, 41 down-regulated), and 52 genes in SKMel-28 (43 up-, 9 down-regulated). CXCL10/IP-10 transcript showed up to 20 fold-increase, with similar changes detectable at the protein level. miRNA expression profiling in cells overexpressing PDGFR-alpha identified 14 miRNAs up- and 40 down-regulated, with miR-503 being the most down-regulated (6.4 fold-reduction). miR-503, miR-630 and miR-424 deregulation was confirmed by qRT-PCR. Interestingly, the most upregulated transcript (i.e., CXCL10/IP-10) was a validated miR-503 target and CXCL10/IP-10 neutralization significantly reverted the anti-proliferative action of PDGFR-alpha, and PDGFR-alpha inhibition by Dasatinb totally reverted the CXCL10/IP10 induction, further supporting a functional interplay of these factors. Finally, integration of transcriptomics and miRNomics data highlighted several pathways affected by PDGFR-alpha.This study demonstrates for the first time that PDGFR-alpha strongly inhibits endothelial and melanoma cells proliferation in a CXCL10/IP-10 dependent way, via miR-503 down-regulation.

| S-EPMC5363585 | biostudies-literature

A novel tree shrew model of lipopolysaccharide-induced acute respiratory distress syndrome.

Project description:IntroductionAcute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development.ObjectivesTo examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features.MethodsLPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells.ResultsResults demonstrated that tree shrews exhibited an average survival time of 3-5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO2 to FiO2 (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with 18F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS.ConclusionThis study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research.

| S-EPMC10834818 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data