Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%). The mechanism of RX-207 action, analyzed by UV spectroscopy, confirmed that which was elucidated for chemically related anti-inflammatory SMIGs. RX-207 binding to cell surface GAGs can account for the inhibition of neutrophil recruitment via the micro-vasculature and as a consequence, the reduction of neutrophil mediated tissue damage in the animal models of inflammation and improved survival of mice in CLP-induced sepsis.
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PMID:RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis. 2911 Jan 54

The possible role of G protein-coupled receptor 39 (GPR39) in inflammation was examined in macrophages. Gpr39 expression increased in thioglycollate-induced peritoneal macrophages. TC-G 1008, a G protein-coupled receptor 39 agonist, enhanced interleukin (IL)-10 production from thioglycollate-induced peritoneal macrophages stimulated with lipopolysaccharide (LPS) in vitro. In addition, the oral administration of TC-G 1008 enhanced serum IL-10 concentrations in an LPS-induced murine model of sepsis. The ablation of G protein-coupled receptor 39 significantly reduced IL-10 production by TC-G 1008 in thioglycollate-induced peritoneal macrophages stimulated with LPS and in the LPS-induced murine model of sepsis. Moreover, the oral administration of TC-G 1008 significantly improved the survival rate in the LPS-induced murine model of sepsis. Taken together, our data suggest that G protein-coupled receptor 39 exhibits an anti-inflammatory activity by enhancing IL-10 production from macrophages.
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PMID:G protein-coupled receptor 39 plays an anti-inflammatory role by enhancing IL-10 production from macrophages under inflammatory conditions. 3005 7

Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.
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PMID:Menstrual blood-derived stromal cells modulate functional properties of mouse and human macrophages. 3328 96


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