The immune system can both promote and suppress cancer. Chronic inflammation and proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are considered tumor-promoting. In contrast, the exact nature of protective antitumor immunity remains obscure. In this study, we have quantified locally secreted cytokines during primary immune responses against myeloma and B-cell lymphoma in mice. Strikingly, successful cancer immunosurveillance mediated by tumor-specific CD4+ T cells was consistently associated with elevated local levels of both proinflammatory (IL-1aplha, IL-1beta, and IL-6) and T helper 1 (Th1)-associated cytokines (interferon-alpha, IL-2, IL-12). Cancer eradication was achieved by a collaboration between tumor-specific Th1 cells and tumor-infiltrating, antigen-presenting macrophages. Th1 cells induced secretion of IL-1? and IL-6 by macrophages. Th1-derived interferon-? was shown to render macrophages directly cytotoxic to cancer cells, and to induce macrophages to secrete the angiostatic chemokines CXCL9/MIG and CXCL10/IP-10. Thus, inflammation, when driven by tumor-specific Th1 cells, may prevent rather than promote cancer.
Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer.
Specimen part
View SamplesTranscriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on day 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.
Genome-wide transcription profile of endothelial cells after cardiac transplantation in the rat.
Sex, Specimen part
View SamplesIn this analysis we have compared the gene expression profiles of lymphatic endothelial cells (LECs) isolated from human intestine (iLECs) versus LECs from human skin (dLECs).
Liprin (beta)1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity.
Specimen part
View SamplesIgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN.
Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesNotch1 is a key regulator of endothelial cell behaviour. This experiment was designed to identify genes regulated by Notch1 signaling in inflammatory activated mouse endothelial cells.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesProinflammatory activation of endothelial cells leads to recruitment of leukocytes by upregulation of adhesion molecules and presentation of chemoattractants. In response to such activation there is also a strong shift in the endothelial expression of Notch ligands, with downregulation of Dll4 and a upregulation of JAG1. To assess whether Jagged1 would affect the endothelial activation profile, we suppressed JAG1 expression during IL-1-induced activation by means of siRNA and performed a genome-wide transcriptome analysis. Our results show for the first time that Jagged1 modulates the transcription profile of activated endothelial cells and describe data that imply a role for Jagged1 in sharpening the inflammatory profile of the vasculature, giving it an edge towards leukocyte recruitment. These findings imply that Jagged1 might be a potential therapeutic target to attenuate inflammation and reduce tissue damage in inflammatory diseases.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesInflammatory activation of endothelial cells enables leukocyte recruitment to tissues. We here investigate how Notch1 signaling affects the transcriptional profile of inflammatory activated human umbilical vein cells.
Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
Specimen part
View SamplesThe goal of this study is to elucidate the influence of treadmill training on transcriptome of the upper lumbar spinal cord after thoracic spinal cord hemisection. mRNA profiles of spinal cords at 23 days-post injury with/without treadmill training were generated. The expression levels of 650 genes in the trained animal were increased ( > 2-fold) compared to untrained animals. Our study represents the detailed analysis of transcriptomes of spinal cord distal to the hemisected lesion after treadmill training, with biologic replicates, generated by RNA-seq technology. Overall design: The effect of training after spinal cord injury (T9) on the transcriptome of intact upper spinal cord was investigated.
Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed.
Specimen part
View Samples