Dataset Information

Resveratrol improves hepatic ischemia-reperfusion injury (HIRI) through inhibiting neutrophils via suppressing ERK signaling pathway

ABSTRACT: Methods: Methods: To better understand the role of resveratrol in the regulation of neutrophils activation and function, neutrophils with or without resveratrol in the expose of LPS were compared in a transcriptome sequencing study. Total RNA was isolated from bone marrow and FACS-separated neutrophils. Transcriptome sequencing libraries were generated using NEBNext® Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and sequenced on an Illumina Hiseq platform (Illumina, San Diego, CA). Sequences were aligned to the reference genome with TopHat and processed with Cufflinks, which quantifies each transcript in each sample using reference annotations produced bythe University of California Santa Cruz UCSC. Differentially expressed genes with a fold change of >=2.0 and p value<0.01 between resveratrol treated and control neutrophils were submitted to GO and KEGG enrichment analysis, which uses unbiased methods to assess pathway enrichment. Results: Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that downregulated genes from resveratrol-stimulated neutrophils are involved in neutrophil migration, neutrophil chemotaxis, TNF signaling pathway and cytokine activity, among other. Compared to control neutrophils, neutrophils with resveratrol exhibited downregulated levels of cell survival related genes (Camkk1, Aqp1, Bcl2a1b, etc), cell cycle related genes (Ccnb1, Ccnb2, Cdc20, Cdk1, etc), adhesion and migration related genes (Cass4, Nectin4, Gp5, Gpr35, etc), and cytokines (Csf1, Csf3, Ccl2, Ccl7, Ccl12).

ORGANISM(S): Mus musculus

PROVIDER: GSE215236 | GEO | 2023/02/09

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Method: To better understand the mechanism of perforin in regulating liver CD8 T cell-mediated inflammation during NASH, we sorted CD8 T cells from the livers of WT or Prf1null mice fed the MCD diet for 4 weeks and performed mRNA sequencing of these hepatic CD8 T cells. Total RNA was isolated from FACS-separated hepatic CD8 T cells. Transcriptome sequencing libraries were generated using NEBNext® Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and sequenced on an Illumina Hiseq platform (Illumina, San Diego, CA). Sequences were aligned to the reference genome with TopHat and processed with Cufflinks, which quantifies each transcript in each sample using reference annotations produced bythe University of California Santa Cruz UCSC. Differentially expressed genes with a fold change of >=2.0 and padj < 0.05 between CD8 T cells from perforin knockout mice or WT mice fed the MCD were submitted to GO and KEGG enrichment analysis, which uses unbiased methods to assess pathway enrichment. Result: Gene Ontology categories (biological processes) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that the DEGs in hepatic CD8 T cells from MCD-fed Prf1null mice are involved in cell adhesion, apoptotic process, cell migration, T cell proliferation, regulation of cytokine secretion, complement and coagulation cascades, etc. Compared with CD8 T cells from the steatotic livers of WT mice, hepatic CD8 T cells from MCD-fed perforin knockout mice showed significantly upregulated levels of anti-apoptotic genes (Ei24, Tnfrsf22, Tnfrsf23, Maf and Siah2), chemokines (Cxcl3), chemokine receptor (Ccr5), genes linked to cell activation (Sfpq and P2rx7), proinflammatory cytokine secretion (C1qtnf1, C1qtnf6, CD36, and Tek) and proinflammatory signaling pathways (Tnfsf12, Tnfsf14, Ptgs2, Mapk3, Mapk7, Mapk12, Il12rb2 and Grb2), and downregulated levels of apoptosis-promoting genes (Dffb and Tnfrsf21).

Project description:Background: We investigated the effect of PPIA overexpression on downstream gene expression at the cellular level. Methods: The PPIA gene was overexpressed in human umbilical vein endothelial cells. Then, transcriptome sequencing was performed. The differentially expressed genes and genes with alternative splicing were screened. GO and KEGG analyses were performed. Nine differentially expressed genes and 7 genes with alternative splicing were validated by real-time quantitative PCR. Results: After PPIA overexpression, 328 genes were differentially expressed, including 157 up-regulated genes and 171 down-regulated genes. GO enrichment analysis of up-regulated genes found that the enriched GO terms included extracellular region, protein binding and metal ion binding, etc. For down-regulated genes, the enriched GO terms included neuron projection, protein binding, endoplasmic reticulum unfolded protein response, etc. KEGG showed that the up-regulated genes were mainly enriched in gastric acid secretion, AMPK signaling pathway, etc; and, the down-regulated genes were enriched in transcriptional misregulation in cancer, TNF signaling pathway, etc. Real-time quantitative PCR analysis of ATF4 (activating transcription factor 4), PPP1R15A (protein phosphatase 1, regulatory (inhibitor) subunit 15A protein phosphate 1, regulatory (inhibitor) subunit 15A), GADD45B (growth arrest and DNA damage inducible protein 45B), SGK1 (serum/glucocorticoid regulated kinase 1), DDIT3 (Recombinant DNA Damage Inducible Transcript 3), PMAIP1 (Phorbol-12-myristate-13-acetate-induced Protein 1), SULF1 (Sulfatase 1), GDF6 (Growth Differentiation Factor 6), and XBP1 (X-Box Binding Protein 1) obtained consistent results with the sequencing results. On the other hand, multiple genes with alternative splicing were identified and analyzed with KEGG and GO. Real-time quantitative PCR validation showed that the probability of alternative splicing in LHPP, APH1A, BRD1, and ORAI3 was increased. However, the changes of NFX1, SERGEF, and PCBP4 were inconsistent with the sequencing results. Conclusion: The overexpression of PPIA in human umbilical vein endothelial cells causes changes in the expression of downstream genes, and induces alternative splicing in multiple genes. PPIA may be involved in the development of atherosclerosis by regulating the expression of downstream genes and causing endothelial cell dysfunction.

Project description:Methods: To better understand the role of OX40 in the regulation of monocyte activation and polarization, OX40/Fc- or control IgG-treated liver monocytes were compared in a transcriptome sequencing study. Total RNA was isolated from FACS-separated hepatic monocytes. Transcriptome sequencing libraries were generated using NEBNext® Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) following manufacturer’s recommendations and sequenced on an Illumina Hiseq platform (Illumina, San Diego, CA). Sequences were aligned to the reference genome with TopHat and processed with Cufflinks, which quantifies each transcript in each sample using reference annotations produced bythe University of California Santa Cruz UCSC. Differentially expressed genes with a fold change of >=2.0 and padj < 0.05 between OX40 treated and control monocytes were submitted to GO and KEGG enrichment analysis, which uses unbiased methods to assess pathway enrichment. Results: Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that upregulated genes from OX40-stimulated monocytes are involved in inflammatory response; cytokine production regulation; lipid, cytokine and bacteria responses; innate immune response; enhanced cellular response to cytokines and the cytokine-cytokine receptor interaction; and the phagosome and chemokine signaling pathway, among others. Compared to control monocytes, OX40/Fc-treated monocytes exhibited upregulated levels of cytokines (Tnf, Il1a, Il1b, Il6 and Il12a), cytokine receptors (Il1rl1, Il2r, Il18r and Il23r), chemokines (Ccl3, Ccl4, Ccl22, Cxcl1, Cxcl2, Cxcl10 and Cx3cl1), chemokine receptors ( Ccrl2, Cxcr5 and Cxcr6) and antigen processing and presentation molecules (Cd40, Cd80, Cd86, Tlr1, Tlr2, and Ox40l). The coordinated action of various inflammatory modulators, signaling molecules, and transcription factors, including Nlrp3, Tank, Jak2, Stat5a, Hif1a, Nos2, Socs3, Mir155hg and Pparg, was determined to be involved in the OX40 regulation of monocyte M1 polarization. MyD88, Irf3, Irf5, Stat1, Nod1 and Nod2 may not be involved in OX40-triggered monocyte M1 polarization.

Dataset Information

Resveratrol improves hepatic ischemia-reperfusion injury (HIRI) through inhibiting neutrophils via suppressing ERK signaling pathway

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure