Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103009 | ENA |
REPOSITORIES: ENA
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Project description:Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation, implicated in numerous diseases including atherosclerosis. We have used primary human monocytes, which express both receptors, to analyze transcriptional responses to LTB4. Comparisons were made between LTB4- and vehicle-treated samples at the same time point. The analysis showed that expression of 72 genes was upregulated at least two-fold at two time points. These genes include multiple chemokines as well as some genes with unknown function. Keywords: time course
2007-10-18 | GSE9332 | GEO
Project description:Gliotoxin (GT), a major secondary metabolite and virulence factor of Aspergillus fumigatus, suppresses innate immunity and supports the evasion of host immune responses. Recently, we revealed that GT blocks leukotriene (LT)B4 formation by directly inhibiting LTA4 hydrolase (LTA4H) in activated human neutrophils and monocytes. Here, we elucidated the impact of GT on LTB4 biosynthesis and the complex lipid mediator network in human M1- and M2-like monocyte-derived macrophage (MDM) subtypes and studied the respective consequences for innate immune cell functions. Notably, in resting MDMs, GT elicited prostaglandin and 12/15-lipoxygenase product formation, although less efficient than bacterial exotoxins. In activated MDM, LTB4 formation was effectively suppressed by GT, connected to impaired macrophage phagocytic activity, and detrimental consequences for neutrophil movement and migration. Conclusively, GT impairs functions of activated innate immune cells through suppression of LTB4 formation, while GT may prime the immune system by provoking prostaglandin formation and 12/15-lipoxygenase-derived LM.
2024-11-13 | PXD045819 | Pride
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with Leukotriene B4 (LTB4) labeled with Cy5- time course with repeats Keywords: ordered
2003-04-14 | GSE390 | GEO
Project description:In this model, naïve blood neutrophils are migrated through a small airway epithelium grown at air-liquid interface toward CF airway fluid supernatant (CFASN, which corresponds to sputum sequentially centrifuged to remove cells and bacteria) or leukotriene B4 (LTB4, transmigration control), placed apically.
2021-02-19 | GSE167069 | GEO
Project description:Nonalcoholic steatohepatitis (NASH) is a prevalent disease that can ultimately progress to more severe forms of disease including liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and ultimately death. A key feature of NASH is lobular inflammation, which is a major driver of disease progression, and both innate and adaptive immune mechanisms support and perpetuate hepatic inflammation in NASH. Previous studies have demonstrated that the pro-inflammatory leukotriene B4 (LTB4) is a potent chemoattractant that drives macrophage and neutrophil chemotaxis, and genetic loss or inhibition of its high affinity receptor, leukotriene B4 receptor 1 (BLT1), results in improved insulin sensitivity and decreased lipid accumulation in the liver. Accordingly, the LTB4-BLT1 axis is a potential therapeutic target for the treatment of liver steatosis and insulin resistance by modulating inflammation.The goal of this study is to validate the therapeutic efficacy of BLT1 inhibition in a NASH mouse model.
2023-11-25 | GSE248273 | GEO
Project description:The objective of this study was to compare the transcriptional repertoire of mature human neutrophils before and after GM-CSF treatment by using oligonucleotide microarrays. Leukotriene B4 (LTB4) is an important pro-inflammatory lipid mediator generated by neutrophils upon activation. Granulocyte/macrophage colony-stimulating factor (GM-CSF) stimulation is known to enhance agonist-mediated LTB4 production of neutrophils within minutes, a process called “priming”. Here, we demonstrate that GM-CSF also limits the production of LTB4 by neutrophils via a transcriptional mechanism at later time points. We identified hematopoietic specific Ras homologous (RhoH)/translocation three four (TTF), which was induced following GM-CSF stimulation in neutrophils, as a key regulator in this process. Neutrophils derived from RhoH/TTF-deficient (Rhoh-/-) mice demonstrated increased LTB4 production upon activation compared with normal mouse neutrophils. Moreover, neutrophils from cystic fibrosis patients expressed enhanced levels of RhoH/TTF and generated less LTB4 upon activation compared with normal human neutrophils. Taken together, these data suggest that RhoH/TTF represents an inducible feedback inhibitor in neutrophils that is involved in the limitation of innate immune responses.
2009-03-31 | GSE15139 | GEO
Project description:Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes
| PRJNA132125 | ENA
Project description:Breast cancer cells facilitate distant metastasis through the induction of immunosuppressive regulatory B cells, designated tBregs. We report here that, to do this, breast cancer cells produce metabolites of the 5-lipoxygenase (5-LO) pathway such as leukotriene B4 (LTB4) to activate the proliferator-activated receptor alpha (PPARalpha) in B cells. Inactivation of LTB4 signaling or genetic deficiency of PPARalpha in B cells blocks the generation of tBregs and thereby abrogates lung metastasis in mice with established breast cancer. Thus, in addition to eliciting fatty acid oxidation and metabolic signals, PPARalpha initiates programs required for differentiation of tBregs. We propose that PPARalpha in B cells or/and tumor 5-LO pathways represents new targets for pharmacological control of tBreg-mediated cancer escape.
2013-03-13 | GSE43278 | GEO
Project description:Timely inhibition of inflammation and initiation of resolution are important for the repair of injured tissues. Pharmacological inhibition of mammalian STE20-like protein kinase 1/2 (MST1/2) with XMU-MP-1 might augment tissue regeneration and repair by suppressing apoptosis and increasing cell proliferation. However, MST1 has anti-inflammatory activity, inhibition of which may result in therapy failure. Here, we identified an approach with the potential to overcome this limitation by protecting against cardiac inflammation resulting from inhibition of MST1 in macrophages. We found exacerbation of cardiac dysfunction in LysMCre-mediated Mst1/2-deficient mice after myocardial infarction (MI). This effect was attributed to a shift of macrophage subtypes from those expressing Cxcl2 and Cd163 toward those with Ccl2 and Ccl4 expression. Mass spectrometry identified leukotriene B4 (LTB4) as the lipid mediator that was upregulated in the absence of MST1. We found that MST1 phosphorylated 5-lipoxygenase (5-LOX) at its T218 residue, disrupting the interaction between 5-LOX and 5-LOX-activating protein, and resulting in reduction of LTB4 production. By contrast, a 5-LOXT218A variant showed no response to MST1. Moreover, treatment of peritoneal macrophages with LTB4 or with medium conditioned by Mst1-deficient macrophages resulted in high Ccl2 and Ccl4 expression and low Cxcl2 and Cd163 expression, except when the cells were co-treated with the LTB4 receptor 1 (BLT1) antagonist CP105696. Furthermore, CP105696 ameliorated cardiac dysfunction in LysMCre-mediated Mst1/2-deficient mice and enhanced cardiac repair in wild-type mice treated with XMU-MP-1 after MI. The combination of an MST1/2 inhibitor and a BLT1 antagonist represents a promising strategy for combatting the effects of MI.
2021-12-13 | GSE181935 | GEO