During systemic inflammation, different neutrophil subsets are mobilized to the blood circulation. These neutrophil subsets can be distinguished from normal circulating neutrophils (CD16bright/CD62Lbright) based on either an immature CD16dim/CD62Lbright or a CD16bright/CD62Ldim phenotype. Interestingly, the latter neutrophil subset is known to suppress lymphocyte proliferation ex vivo, but the underlying mechanism is largely unknown.
IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1.
Specimen part, Disease, Disease stage, Treatment
View SamplesPolymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have investigated gene transcription during experimental endotoxemia in whole blood and peripheral blood mononuclear cells. However, the gene transcription response of the circulating pool of neutrophils to systemic inflammatory stimulation in vivo is currently unclear. We examined neutrophil gene transcription kinetics in healthy human subjects (n=4) administered a single dose of endotoxin (LPS, 2 ng/kg iv). In addition, freshly isolated neutrophils were stimulated ex vivo with LPS, TNF, G-CSF and GM-CSF to identify stimulus-specific gene transcription responses. Whole transcriptome microarray analysis of circulating neutrophils at 2, 4 and 6 hours after LPS infusion revealed activation of inflammatory networks which are involved in signaling of TNF and IL-1 and IL-1. The transcriptome profile of inflammatory activated neutrophils in vivo reflects extended survival and regulation of inflammatory responses. We show that these changes in neutrophil transcriptome are most likely due to a combination of early activation of circulating neutrophils by TNF and G-CSF and a mobilization of young neutrophils from the bone marrow.
Transcriptome kinetics of circulating neutrophils during human experimental endotoxemia.
Specimen part
View SamplesInnate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as LPS. We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time dependent manner. ChIP-seq, RNA-seq, WGBS and ATAC-seq data were generated. This analysis identified epigenetic programs in tolerance and trained macrophages, and the potential transcription factors involved. Overall design: Time-course in vitro culture of human monocytes. Two innate immune memory states can be induced in culture through an initial exposure of primary human monocytes to either LPS or BG for 24 hours, followed by removal of stimulus and differentiation to macrophages for an additional 5 days. Cells were collected at baseline (day 0), 1 hour, 4 hour, 24 hour and 6 days.
β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance.
Specimen part, Treatment, Subject
View SamplesMicroRNA microarrays and RNA expression arrays were used to identify functional signaling between neural stem cell progenitor cells (NSPC) and brain endothelial cells (EC) that are critical during embryonic development and tissue repair following brain injury.
The role of microRNAs in neural stem cell-supported endothelial morphogenesis.
Specimen part, Disease, Treatment
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View SamplesWe investigate the role of Snf2l in ovaries by characterizing a mouse bearing an inactivating deletion on the ATPase domain of Snf2l (Ex6DEL). Snf2l mutant mice produce significantly fewer eggs than control mice when superovulated. Thus, gonadotropin stimulation leads to a significant deficit in secondary follicles and an increase in abnormal antral follicles. We profiled the expression of granulosa cells from Snf2l WT and Ex6DEL mice treated with pregnant mares' serum gonadotropin followed by human chorionic gonadotropin
The imitation switch ATPase Snf2l is required for superovulation and regulates Fgl2 in differentiating mouse granulosa cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of the cortical neurons that mediate antidepressant responses.
Specimen part, Treatment
View SamplesMicroarrays were used to analyze differential gene expression and to help determine the efficacy of Iressa (gefitinib), a tyrosine kinase inhibitor, on endometrial cancer cells.
EGFR isoforms and gene regulation in human endometrial cancer cells.
Specimen part, Cell line
View SamplesNine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours.
Effects of 10 cigarette smoke condensates on primary human airway epithelial cells by comparative gene and cytokine expression studies.
Specimen part
View SamplesMolecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment.
Identification of the cortical neurons that mediate antidepressant responses.
Specimen part, Treatment
View Samples