Time course study of the response to LPS targeting the pig immune response gene networks
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PROVIDER: PRJNA420347 | ENA |
REPOSITORIES: ENA
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Project description:To explore individual variation in the biological response to a systemic challenge in pigs, we have developed a microarray analysis to study the kinetics of the response to a lipopolysaccharide (LPS) injection measured at 4 time points. LPS is a major component of the outer membrane in gram-negative bacteria. LPS provokes an acute inflammatory syndrome resulting eventually in all kinds of pathophysiological damages. The objective was to identify genes up- or down-regulated during the stress response triggered by LPS in the whole blood.
2017-11-30 | GSE107487 | GEO
Project description:Mouse bone marrow-derived macrophages (BMDM) grown in macrophage colony-stimulating factor (CSF-1) have been used widely in studies of macrophage biology and the response to toll-like receptor agonists. We investigated whether similar cells could be derived from the domestic pig. Cultivation of pig bone marrow cells for 5-7 days in presence of rhCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, CD163, CD172a), are potent phagocytic cells and produced tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS). Bone marrow cells could be stored frozen and thawed, providing a renewable resource. We profiled gene expression in pig BMDM from outbred animals (Large-White Landrace F1cross) responding to LPS using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely-resembled human than mouse macrophages, and included genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20) and the vitamin D3-converting enzyme Cyp27B1. Conversely, pig BMDM, like human macrophages, did not induce genes involved in arginine metabolism, nor did they produce nitric oxide. The data establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control.
2011-09-01 | GSE30956 | GEO
Project description:Mouse bone marrow-derived macrophages (BMDM) grown in macrophage colony-stimulating factor (CSF-1) have been used widely in studies of macrophage biology and the response to toll-like receptor agonists. We investigated whether similar cells could be derived from the domestic pig. Cultivation of pig bone marrow cells for 5-7 days in presence of rhCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, CD163, CD172a), are potent phagocytic cells and produced tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS). Bone marrow cells could be stored frozen and thawed, providing a renewable resource. We profiled gene expression in pig BMDM from outbred animals (Large-White Landrace F1cross) responding to LPS using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely-resembled human than mouse macrophages, and included genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20) and the vitamin D3-converting enzyme Cyp27B1. Conversely, pig BMDM, like human macrophages, did not induce genes involved in arginine metabolism, nor did they produce nitric oxide. The data establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control. RNA for gene expression analysis was collected at time points 0, 2, 7 and 24 hours post LPS stimulation (100ng/ml). Each time point included BMDM from the same three pigs and each cell culture was replicated. The replicate of the pig3_24h was not suitable for RNA analysis. Therefore, a total of 23 microarrays were hybridized.
2011-08-31 | E-GEOD-30956 | biostudies-arrayexpress
Project description:Stress is a generic term used to describe non-specific responses of the body to all kinds of challenges. A very large variability in the response can be observed across individuals, depending on numerous conditioning factors like genetics, early influences and life history. As a result, there is a wide range of individual vulnerability and resilience to stress, also called robustness. The importance of robustness-related traits in breeding strategies is increasing progressively towards the production of animals with a high level of production under a wide range of climatic conditions and management systems, together with a lower environmental impact and a high level of animal welfare. The present study aims at describing blood transcriptomic, hormonal, and metabolic responses of pigs to a systemic challenge using lipopolysaccharide (LPS). The objective is to analyze the individual variation of the biological responses in relation to the activity of the HPA axis measured by the levels of plasma cortisol after LPS and ACTH in 120 juvenile Large White (LW) pigs. The kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data.Cortisol level reaches its peak 4 h after LPS injection. The characteristic changes of white blood cell count to LPS were observed, with a decrease of total count, maximal at t=+4 h, and the mirror changes in the respective proportions of lymphocytes and granulocytes. The lymphocytes / granulocytes ratio was maximal at t=+1 h. An integrative statistical approach was used and provided a set of candidate genes for kinetic studies and ongoing complementary studies focused on the LPS-stimulated inflammatory response.The present study demonstrates the specific biomarkers indicative of an inflammation in swine. Furthermore, these stress responses persist for prolonged periods of time and at significant expression levels, making them good candidate markers for evaluating the efficacy of anti-inflammatory drugs.
| S-EPMC5741867 | biostudies-literature
Project description:cDNA microarray study of gene expression changes in whole blood from LPS treated rats, 2 and 6 hours after I.P. injection of 5 mg/kg Keywords: time-course
2005-02-09 | GSE1658 | GEO
Project description:RNA sequencing of pig (Sus scrofa) bone marrow derived macrophages (BMDMs), both unstimulated and 7 hours after stimulation with lipopolysaccharide (LPS).
| PRJEB22536 | ENA
Project description:LPS response during systemic infection
| PRJNA378232 | ENA
Project description:LPS time-course in WT and Stk40 KO BMDMs
| PRJNA511979 | ENA
Project description:Molecular Pathways and Transcriptional Networks Involved in the Macrophage Response to LPS, poly(I:C) and CpG DNA Stimulation Background: Toll-like family of receptors recognizes pathogen-associated molecular patterns (PAMPs) from different organisms. TLR4 is the receptor for bacterial lipopolysaccharide (LPS), dsRNA viral mimic poly(I:C) binds to TLR3, and bacterial CpG DNA signals through TLR9. TLR4 signaling is mediated by adaptor molecules Myd88 and TRIF while TLR3 pathway involves only the TRIF adaptor and TLR9 signals solely through Myd88. Methods: To identify genes other than those in TLR pathways that mediate macrophage response to different PAMPs, RAW264.7 cells were stimulated with LPS, poly(I:C), or CpG DNA, and RNA was profiled on microarrays 6 hrs and 24 hrs post-treatment. Gene expression data were analyzed to determine genes, pathways and transcriptional networks that are in common and unique to each of the three TLR stimuli. Potentially novel candidates revealed by this analysis were tested for their role in innate immunity using RNA interference. Results: Many genes are differentially regulated by LPS and poly(I:C) at both 6 hrs and 24 hrs following treatment, while CpG DNA elicits a much less pronounced transcriptional response. By analyzing gene expression data for networks and pathways, we prioritized differentially expressed genes that are in common to all three PAMPs as well as those shared by LPS and poly(I:C). Knockdown by RNA interference of two genes, Plec1 and TPST1, inhibited production of IL-6 in response to LPS in cultured macrophages. Conclusions: We have identified novel innate immunity genes that may be important in macrophage response to LPS, poly(I:C), and CpG DNA stimuli. Our results provide potential biomarkers and therapeutic targets that should be further investigated in mice and human populations.
2009-07-01 | GSE15066 | GEO
Project description:pan-Kinase degrader response time course
| PRJNA661753 | ENA