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Spleen vs Leukotriene B4 (LTB4) Treated B cell

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE390 | GEO | 2003/04/14

SECONDARY ACCESSION(S): PRJNA84917

REPOSITORIES: GEO

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Study of Leukotriene B4 (LTB4) effect on primary human monocytes transcription profile

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

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Leukotriene B4 receptor 1 antagonist in combination with kinase MST1/2 inhibitor has potential for treatment of myocardial infarction

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.

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Cooperative and redundant signaling of leukotriene B4 and leukotriene D4 in human monocytes

Project description:LTB4, 50 nmol/L for 30 minutes, induced expression of 27 genes in cultured human elutriated monocytes comparred to vehicle (ethanol) treated control cells. Matched control versus treated cells

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Spleen vs Untreated, cultured B cell

Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells untreated and cultured, labeled with Cy5- time course with repeats Keywords: ordered

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Spleen vs Terbutaline Treated B cell

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Spleen vs IL4 Treated B cell

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 IL4 labeled with Cy5- time course with repeats Keywords: ordered

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Spleen vs fMLP Treated B cell

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 fMLP labeled with Cy5- time course with repeats Keywords: ordered

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Spleen vs ELC Treated B cell

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 ELC labeled with Cy5- time course with repeats Keywords: ordered

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