Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells.
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.
Viemann
Dorothee
D
Institute 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
Strey
Anke
A
Janning
Annette
A
Jurk
Kerstin
K
Klimmek
Kerstin
K
Vogl
Thomas
T
Hirono
Keiichi
K
Ichida
Fukiko
F
Foell
Dirk
D
Kehrel
Beate
B
Gerke
Volker
V
Sorg
Clemens
C
Roth
Johannes
J
D040501:Calgranulin A / Q000235:genetics / Q000276:immunology*; D040502:Calgranulin B / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D002196:Capillaries / Q000166:cytology / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007365:Intercellular Junctions / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013927:Thrombosis / Q000276:immunology; D014657:Vasculitis / Q000276:immunology* / Q000503:physiopathology*
D040501:Calgranulin A; D040502:Calgranulin B; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1