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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells
Dorothee Viemann1, Anke Strey, Annette Janning
1Institute of Experimental Dermatology, Integrated Functional Genomics, and the Interdisciplinary Clinical Research Center, University Hospital Muenster, University of Muenster, Röntgenstrasse 21, 48149 Muenster, Germany. viemannd@uni-muenster.de
Abstract:
Myeloid-related protein 8 (MRP8) and MRP14, S100 proteins secreted by activated phagocytes, bind specifically to endothelial cells. The endothelial response to MRP8/MRP14, however, is unknown. Using oligonucleotide microarray analysis, we show for the first time that MRP8/MRP14 induce a thrombogenic, inflammatory response in human microvascular endothelial cells by increasing the transcription of proinflammatory chemokines and adhesion molecules and by decreasing the expression of cell junction proteins and molecules involved in monolayer integrity. All changes on the gene expression level could be confirmed using biochemical and functional assays. We demonstrated that the expression of MRP8/MRP14 closely correlated with the inflammatory activity in systemic vasculitis, confirming the important role of these proteins for distinct inflammatory reactions in endothelia. MRP8/MRP14 may represent novel targets for anti-inflammatory strategies.
Insights
Myeloid-related proteins (MRP8/MRP14) trigger inflammation and clotting in endothelial cells. These S100 proteins, elevated in vasculitis, may be targets for anti-inflammatory therapies.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Myeloid-related protein 8 (MRP8) and MRP14 are S100 proteins secreted by activated phagocytes.
- These proteins bind to endothelial cells, but their specific effects on endothelial cells are not well understood.
Purpose of the Study:
- To investigate the endothelial cell response to MRP8/MRP14.
- To determine the role of MRP8/MRP14 in inflammatory conditions.
Main Methods:
- Oligonucleotide microarray analysis was used to assess gene expression changes in human microvascular endothelial cells.
- Biochemical and functional assays were employed to confirm gene expression findings.
- MRP8/MRP14 expression levels were correlated with inflammatory activity in systemic vasculitis.
Main Results:
- MRP8/MRP14 significantly altered gene expression in endothelial cells, promoting a thrombogenic and inflammatory profile.
- Key changes included increased transcription of pro-inflammatory chemokines and adhesion molecules.
- Decreased expression of cell junction proteins and molecules maintaining monolayer integrity was observed.
- MRP8/MRP14 expression correlated with inflammatory activity in systemic vasculitis.
Conclusions:
- MRP8/MRP14 induce a pro-thrombotic and inflammatory response in endothelial cells.
- These proteins play a significant role in endothelial inflammatory reactions, particularly in systemic vasculitis.
- MRP8/MRP14 represent potential novel therapeutic targets for anti-inflammatory strategies.
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