The interferon-inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response.
The IFN-inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site-specific mutation demonstrated that NF-κB is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-lymphocyte migration triggered by supernatants from IFI16-overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation.
Baggetta
Rossella
R
Department of Public Health and Microbiology, Medical School of Turin, Turin, Italy.
De Andrea
Marco
M
Gariano
Grazia Rosaria
GR
Mondini
Michele
M
Rittà
Massimo
M
Caposio
Patrizia
P
Cappello
Paola
P
Giovarelli
Mirella
M
Gariglio
Marisa
M
Landolfo
Santo
S
D019138:Antibodies, Blocking / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D040081:Protein Array Analysis; D015533:Transcriptional Activation
D019138:Antibodies, Blocking; D054418:Chemokine CCL20; D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human