Journal
JOURNAL OF MOLECULAR MEDICINE-JMM
Volume 88, Issue 10, Pages 1065-1079Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-010-0648-8
Keywords
Monocytes; Inflammation; Transcriptomics; TNF-alpha; LPS
Funding
- German Ministry of Education and Research (BMBF) within the National Genome Research Network NGFN [01GS0413]
- European Union [LSHB-CT-2006-018861]
Ask authors/readers for more resources
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-alpha) 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-alpha and LPS resulted in 4,529 and 5,036 differentially expressed genes, respectively. Although both stimuli induced similar inflammatory profiles in monocytes, TNF-alpha- 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available