A Novel Role of the Interferon-inducible Protein IFI16 as Inducer of Proinflammatory Molecules in Endothelial Cells

Caposio, Patrizia; Gugliesi, Francesca; Zannetti, Claudia; Sponza, Simone; Mondini, Michele; Medico, Enzo; Hiscott, John; Young, Howard A.; Gribaudo, Giorgio; Gariglio, Marisa; Landolfo, Santo

doi:10.1074/jbc.m701846200

Cited by 68 publications

(76 citation statements)

References 47 publications

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“…This domain was identified as a putative protein-protein interaction domain at the N-terminus of several other proteins believed to function in inflammatory signalling pathways. Consistent with these observations, prominent in vivo IFI16 expression has been demonstrated in lymphocytes, monocytes, stratified squamous epithelia and endothelial cells (EC) isolated from both blood and lymph vessels [8,9], suggesting a role for IFI16 in the modulation of inflammation and the immune response. We have previously shown that IFI16 overexpression in EC triggered at the transcriptional level the expression of both adhesion molecules (such as ICAM-1) and chemokines (such as CCL2 and CCL20) [9].…”

Section: Introductionmentioning

confidence: 51%

“…Consistent with these observations, prominent in vivo IFI16 expression has been demonstrated in lymphocytes, monocytes, stratified squamous epithelia and endothelial cells (EC) isolated from both blood and lymph vessels [8,9], suggesting a role for IFI16 in the modulation of inflammation and the immune response. We have previously shown that IFI16 overexpression in EC triggered at the transcriptional level the expression of both adhesion molecules (such as ICAM-1) and chemokines (such as CCL2 and CCL20) [9]. The treatment of cells with short hairpin RNA, targeting IFI16 significantly inhibited ICAM-1 induction by IFN-g demonstrating that IFI16 is required for proinflammatory gene stimulation by this cytokine.…”

Section: Introductionmentioning

confidence: 51%

“…We have previously analyzed transcriptomes from EC overexpressing IFI16 and found that IFI16 upregulates a complex array of cellular genes encoding inflammatory molecules responsible for leukocyte recruitment [9]. Moreover, we showed that IFI16 triggers the expression of EC ICAM-1 [9] -an adhesion molecule involved in the enrolment of cells at the site of inflammation during the first steps of inflammation [13].…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, we showed that IFI16 triggers the expression of EC ICAM-1 [9] -an adhesion molecule involved in the enrolment of cells at the site of inflammation during the first steps of inflammation [13]. In this study, in order to determine whether IFI16 also induces the secretion of chemokines and cytokines, we first analyzed the IFI16 secretome for 174 common chemokines, cytokines and growth factors using RayBio human cytokine array G Series 2000 Ab arrays.…”

Section: Resultsmentioning

confidence: 99%

“…Previous results have demonstrated that NF-kB is the main mediator of IFI16-driven ICAM-1 induction responsible for leukocyte adhesion to the endothelium [9]. To determine whether the interaction of IFI16 with NF-kB may also be responsible for the induction of other genes within the IFI16 secretome, functional analysis of the CCL20 gene promoter was performed.…”

Section: Resultsmentioning

confidence: 99%

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The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

et al. 2010

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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-jB 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.

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Section: Introductionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

et al. 2010

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Mediation of Chondrogenic and Osteogenic Differentiation by an Interferon-Inducible p202 Protein

Kong

Liu

2008

Cell. Mol. Life Sci.

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p202, an interferon-inducible protein that belongs to an interferon-inducible p200 family, was highly induced in the course of osteogenesis of pluripotent C2C12 cells and the chondrogenesis of C3H10T1/2 cells. Differential expression of p202 is probably due, at least in part, to the transactivation of the p202 gene by Smad transcription factors. Overexpressing p202 inhibited, whereas lowering p202 via a siRNA approach enhanced, chondrocyte differentiation. In contrast, overexpression of p202 enhanced, whereas knockdown of p202 inhibited, osteoblast differentiation. Molecular mechanism studies revealed that p202 and parathyroid hormone-related peptide (PTHrP) formed a positive feedback loop, since (1) overexpressing p202 markedly enhanced whereas knocking down p202 suppressed the expression of PTHrP; and (2) p202 expression was increased in growth plate chondrocytes of PTHrP receptor transgenic mouse embryos; however, its expression was reduced in PTHrP knockout mouse embryos. Taken together, our findings demonstrate that p202 protein is a novel, important mediator of chondrogenic and osteogenic differentiation.

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Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases

Wang

Bai

2022

Mol Cell Biochem

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A Novel Role of the Interferon-inducible Protein IFI16 as Inducer of Proinflammatory Molecules in Endothelial Cells

Cited by 68 publications

References 47 publications

The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response

Mediation of Chondrogenic and Osteogenic Differentiation by an Interferon-Inducible p202 Protein

Functions and roles of IFIX, a member of the human HIN-200 family, in human diseases

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