TY - JOUR
T1 - The interferon-inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response
AU - Baggetta, Rossella
AU - De Andrea, Marco
AU - Gariano, Grazia Rosaria
AU - Mondini, Michele
AU - Rittà, Massimo
AU - Caposio, Patrizia
AU - Cappello, Paola
AU - Giovarelli, Mirella
AU - Gariglio, Marisa
AU - Landolfo, Santo
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - Chemokines
KW - IFI16
KW - IFN
KW - Inflammation
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UR - http://www.scopus.com/inward/citedby.url?scp=77956131975&partnerID=8YFLogxK
U2 - 10.1002/eji.200939995
DO - 10.1002/eji.200939995
M3 - Article
C2 - 20480502
AN - SCOPUS:77956131975
SN - 0014-2980
VL - 40
SP - 2182
EP - 2189
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 8
ER -