期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 8, 页码 2182-2189出版社
WILEY
DOI: 10.1002/eji.200939995
关键词
Chemokines; IFI16; IFN; Inflammation
类别
资金
- Regione Piemonte
- Italian Ministry for University MIUR
- Fondazione CRT
- Fondazione Italiana per la Ricerca sul Cancro
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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-kappa B is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B-Iymphocyte 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.
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