Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation.

ABSTRACT: Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/NF-κB-mediated cellular reprogramming toward an inflammatory phenotype both in vitro and in vivo. Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Importantly, enhanced sMR levels increase serum proinflammatory cytokines, activate tissue macrophages, and promote insulin resistance. Altogether, our results reveal sMR as regulator of proinflammatory macrophage activation, which could constitute a therapeutic target for metaflammation and other hyperinflammatory diseases.

SUBMITTER: Embgenbroich M

PROVIDER: S-EPMC8346872 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Serum mannose receptor promotes pro-inflammatory macrophage activation and obesity-associated metaflammation

Project description:Elevated serum concentrations of the soluble mannose receptor (sMR) have been reported to correlate with the severity of various inflammatory diseases. A physiological role of sMR, however, remains unclear. Here, we show that sMR binds CD45 on macrophages, both in vitro and in vivo, leading to cellular reprogramming towards an inflammatory phenotype by inhibition of CD45 phosphatase activity, which induces Src/Akt/NF-κB-mediated signaling. Remarkably, increased serum sMR levels correlate with obesity in both mice and humans. In addition, MR deficiency lowers the high-fat diet-induced increase in pro-inflammatory macrophages in metabolic tissues and protects against hepatic steatosis and whole-body metabolic dysfunctions. Conversely, administration of sMR induces serum pro-inflammatory cytokines and pro-inflammatory macrophages in the liver and promote insulin resistance. Altogether, our results reveal sMR as novel regulator of pro-inflammatory macrophage activation and could constitute a novel therapeutic target for hyperinflammatory diseases.

2021-07-16 | GSE145369 | GEO

Serum mannose receptor promotes pro-inflammatory macrophage activation and obesity-associated metaflammation

Project description:Serum mannose receptor promotes pro-inflammatory macrophage activation and obesity-associated metaflammation

| PRJNA606969 | ENA

Macrolide derivatives reduce proinflammatory macrophage activation and macrophage-mediated neurotoxicity.

Project description:IntroductionAzithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.AimsTo improve the efficacy and reduce antibiotic resistance risk of AZM-based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow-derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF-gamma) with and without derivative costimulation. Pro- and anti-inflammatory cytokine production, IL-12 and IL-10, respectively, was quantified using ELISA. Neuron culture treatment with BMDM supernatant was used to assess derivative neuroprotective potential.ResultsAzithromycin and some derivatives increased IL-10 and reduced IL-12 production of M1 macrophages. IL-10/IL-12 cytokine shifts closely correlated with the ability of AZM and derivatives to mitigate macrophage neurotoxicity.ConclusionsSugar moieties that bind bacterial ribosomal complexes can be modified in a manner that retains AZM immunomodulation and neuroprotection. Since the effects of BMDMs in vitro are predictive of CNS macrophage responses, our results open new therapeutic avenues for managing maladaptive CNS inflammation and support utilization of IL-10/12 cytokine profiles as indicators of macrophage polarization and neurotoxicity.

| S-EPMC6488883 | biostudies-literature

ANT2 drives proinflammatory macrophage activation in obesity.

Project description:Macrophage proinflammatory activation is an important etiologic component of the development of insulin resistance and metabolic dysfunction in obesity. However, the underlying mechanisms are not clearly understood. Here, we demonstrate that a mitochondrial inner membrane protein, adenine nucleotide translocase 2 (ANT2), mediates proinflammatory activation of adipose tissue macrophages (ATMs) in obesity. Ant2 expression was increased in ATMs of obese mice compared with lean mice. Myeloid-specific ANT2-knockout (ANT2-MKO) mice showed decreased adipose tissue inflammation and improved insulin sensitivity and glucose tolerance in HFD/obesity. At the molecular level, we found that ANT2 mediates free fatty acid-induced mitochondrial permeability transition, leading to increased mitochondrial reactive oxygen species production and damage. In turn, this increased HIF-1α expression and NF-κB activation, leading to proinflammatory macrophage activation. Our results provide a previously unknown mechanism for how obesity induces proinflammatory activation of macrophages with propagation of low-grade chronic inflammation (metaflammation).

| S-EPMC8564915 | biostudies-literature

OGT suppresses macrophage proinflammatory activation

Project description:OGT suppresses macrophage proinflammatory activation

| PRJNA607991 | ENA

OGT suppresses macrophage proinflammatory activation

Project description:Overnutrition leads to metabolic disorders such as obesity and diabetes. Enhanced inflammation has also been shown to be an essential player in the progression of metabolic diseases. However, how immune cells sense nutritional status and contribute to whole-body metabolism remain largely elusive. OGT-catalyzed protein O-GlcNAcylation is thought to be a metabolic sensor that modulates cell signaling. In this study, we show that overnutrition stimulates macrophage O-GlcNAc signaling. O-GlcNAc signaling suppresses macrophage proinflammatory activation and protects against diet-induced obesity and metabolic dysfunction. These findings thus identify macrophage O-GlcNAc signaling as a novel homeostatic regulator at the interface of inflammation and metabolism.

2020-07-22 | GSE145720 | GEO

NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation.

Project description:Metabolic reprogramming is implicated in macrophage activation, but the underlying mechanisms are poorly understood. Here, we demonstrate that the NOTCH1 pathway dictates activation of M1 phenotypes in isolated mouse hepatic macrophages (HMacs) and in a murine macrophage cell line by coupling transcriptional upregulation of M1 genes with metabolic upregulation of mitochondrial oxidative phosphorylation and ROS (mtROS) to augment induction of M1 genes. Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. As such, inhibition of the NOTCH pathway or Pdp1 knockdown abrogated glucose oxidation, mtROS, and M1 gene expression. Conditional NOTCH1 deficiency in the myeloid lineage attenuated HMac M1 activation and inflammation in a murine model of alcoholic steatohepatitis and markedly reduced lethality following endotoxin-mediated fulminant hepatitis in mice. In vivo monocyte tracking further demonstrated the requirement of NOTCH1 for the migration of blood monocytes into the liver and subsequent M1 differentiation. Together, these results reveal that NOTCH1 promotes reprogramming of mitochondrial metabolism for M1 macrophage activation.

| S-EPMC4396469 | biostudies-literature

Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-acquired Pneumonia.

Project description:CD206, a mannose receptor, is mainly expressed on the surface of alternatively activated macrophages where it acts as a pattern recognition receptor and plays a role in innate and adaptive immunity. This study investigated serum soluble CD206 (sCD206) levels in community-acquired pneumonia (CAP) and examined their clinical significance. sCD206 concentrations were measured in the sera of two independent cohorts with CAP (127 and 125 patients, respectively) and 42 controls. The expression of CD206 in the lung from autopsied cases was also examined. Patients with CAP showed significantly elevated sCD206 levels than did the controls (p?<?0.0001). Notably, fatal CAP patients had more than two-fold higher sCD206 concentrations than survivors in both cohorts (p?<?0.0001). Serum sCD206 concentrations were associated with Pneumonia Severity Index (PSI) and CURB-65 values. Importantly, even fatal CAP patients classified as PSI I-IV, CURB65 0-2 or age <75 years had comparatively higher levels of sCD206 than those classified as PSI V, CURB-65 3-5 or age ?75 years. Immunohistochemically, the infiltration of CD206+ macrophages was found in the lungs of fatal cases. Elevated levels of sCD206 are associated with CAP prognosis, suggesting sCD206 might be a potential biomarker to predict severity for CAP.

| S-EPMC6904766 | biostudies-literature

VSIG4 inhibits proinflammatory macrophage activation by reprogramming mitochondrial pyruvate metabolism.

Project description:Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear. Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide. Vsig4 -/- mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation. VSIG4 activates the PI3K/Akt-STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, mitochondrial reactive oxygen species secretion, and macrophage inhibition. Conversely, interruption of Vsig4 or Pdk2 promotes inflammation. Forced expression of Vsig4 in mice ameliorates MHV-3-induced viral fulminant hepatitis. These data show that VSIG4 negatively regulates macrophage activation by reprogramming mitochondrial pyruvate metabolism.

| S-EPMC5673889 | biostudies-other

Toxoplasma gondii Chitinase Induces Macrophage Activation.

Project description:Toxoplasma gondii is an obligate intracellular protozoan parasite found worldwide that is able to chronically infect almost all vertebrate species, especially birds and mammalians. Chitinases are essential to various biological processes, and some pathogens rely on chitinases for successful parasitization. Here, we purified and characterized a chitinase from T. gondii. The enzyme, provisionally named Tg_chitinase, has a molecular mass of 13.7 kDa and exhibits a Km of 0.34 mM and a Vmax of 2.64. The optimal environmental conditions for enzymatic function were at pH 4.0 and 50 °C. Tg_chitinase was immunolocalized in the cytoplasm of highly virulent T. gondii RH strain tachyzoites, mainly at the apical extremity. Tg_chitinase induced macrophage activation as manifested by the production of high levels of pro-inflammatory cytokines, a pathogenic hallmark of T. gondii infection. In conclusion, to our knowledge, we describe for the first time a chitinase of T. gondii tachyzoites and provide evidence that this enzyme might influence the pathogenesis of T. gondii infection.

| S-EPMC4684212 | 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