Defining TNF-α- and LPS-induced gene signatures in monocytes to unravel the complexity of peripheral blood transcriptomes in health and disease
| Autor: | Bruno Stuhlmüller, Biljana Smiljanovic, Ria Baumgrass, Thomas Häupl, Andreas Grützkau, Andreas Radbruch, Gerd R Burmester, Marta Steinbrich-Zöllner, Joachim R. Grün |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Lipopolysaccharides Male Cell type Lipopolysaccharide medicine.medical_treatment Inflammation Biology Monocytes Transcriptome chemistry.chemical_compound Young Adult Drug Discovery Gene expression medicine Cluster Analysis Humans Genetics (clinical) Whole blood Oligonucleotide Array Sequence Analysis Tumor Necrosis Factor-alpha Monocyte Gene Expression Profiling medicine.anatomical_structure Cytokine chemistry Immunology Molecular Medicine Female medicine.symptom |
| Zdroj: | Journal of molecular medicine (Berlin, Germany). 88(10) |
| ISSN: | 1432-1440 |
| Popis: | Several genome-wide transcriptome studies have shown that chronic inflammatory responses generally taking place in the inflamed tissue are also reflected at the level of peripheral blood leukocytes. Blood monocytes are highly sensitized cell type continuously activated under inflammatory conditions. For a better understanding of the transcriptional imprinting influenced by a multitude of pro- and anti-inflammatory mediators, we established a whole blood in vitro system to explore cell- and stimulus-specific gene expression signatures in peripheral monocytes. In an explorative study, whole blood from healthy donors was stimulated with tumour necrosis factor-alpha (TNF-α) or lipopolysaccharide (LPS) for 1.5 h. Subsequently, monocytes were isolated with a purity of >99% by high-speed fluorescence activated cell sorting. Transcriptional changes were explored by whole genome Affymetrix arrays using highly validated filtering algorithm to identify differentially expressed genes. In vitro stimulation of whole blood samples with TNF-α and LPS resulted in 4,529 and 5,036 differentially expressed genes, respectively. Although both stimuli induced similar inflammatory profiles in monocytes, TNF-α- or LPS-specific gene signatures were characterized. Functional classification identified significant numbers of differentially expressed cytokines, cytokine receptors and apoptosis-associated genes. To our knowledge, this is the first study presenting cell- and stimulus-specific gene expression signatures that can be used to decipher complex disease specific profiles of acute and chronic inflammation. Once a library of signatures from the most important inflammatory mediators is defined, it can be helpful to identify those signatures, which are predominantly driving the disease pathogenesis and which are of potential interest for a therapeutical intervention. |
| Databáze: | OpenAIRE |
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