Endothelial TNF Receptor 2 Induces IRF1 Transcription Factor-Dependent Interferon-β Autocrine Signaling to Promote Monocyte Recruitment

Venkatesh, Deepak; Ernandez, Thomas; Rosetti, Florencia; Batal, Ibrahim; Culleré, Xavier; Luscinskas, Francis W.; Zhang, Yuzhi; Stavrakis, George; García‐Cardeña, Guillermo; Horwitz, Bruce H.; Mayadas, Tanya N.

doi:10.1016/j.immuni.2013.01.012

Cited by 109 publications

(128 citation statements)

References 49 publications

(58 reference statements)

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“…*P < 0.05; **P < 0.001;***P < 0.0001. a view, work has shown that IFNAR1-deficient mice are resistant to TNF-α-induced shock in vivo (27). Consistent with our observations, this pathway of TNF-α-induced IFN-β expression has been demonstrated to occur through an IRF-1-dependent mechanism (38) and appears to occur within endothelial cells as well as macrophages (39). Underlining the importance of IFNAR1, we also have observed that LPS-or polyI:C-induced necroptosis of macrophages is unaffected by the lack of TNFR1/2 but is highly dependent on IFNAR1 expression.…”

Section: Discussionsupporting

confidence: 91%

Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages

McComb

Cessford

Alturki

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

158

139

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Myeloid cells play a critical role in perpetuating inflammation during various chronic diseases. Recently the death of macrophages through programmed necrosis (necroptosis) has emerged as an important mechanism in inflammation and pathology. We evaluated the mechanisms that lead to the induction of necrotic cell death in macrophages. Our results indicate that type I IFN (IFN-I) signaling is a predominant mechanism of necroptosis, because macrophages deficient in IFN-α receptor type I (IFNAR1) are highly resistant to necroptosis after stimulation with LPS, polyinosinicpolycytidylic acid, TNF-α, or IFN-β in the presence of caspase inhibitors. IFN-I-induced necroptosis occurred through both mechanisms dependent on and independent of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) and led to persistent phosphorylation of receptor-interacting protein 3 (Rip3) kinase, which resulted in potent necroptosis. Although various IFN-regulatory factors (IRFs) facilitated the induction of necroptosis in response to IFN−β, IRF-9-STAT1-or -STAT2-deficient macrophages were highly resistant to necroptosis. Our results indicate that IFN-β-induced necroptosis of macrophages proceeds through tonic IFN-stimulated gene factor 3 (ISGF3) signaling, which leads to persistent expression of STAT1, STAT2, and IRF9. Induction of IFNAR1/ Rip3-dependent necroptosis also resulted in potent inflammatory pathology in vivo. These results reveal how IFN-I mediates acute inflammation through macrophage necroptosis.

show abstract

Section: Discussionsupporting

confidence: 91%

Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages

McComb

Cessford

Alturki

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

158

139

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“…A role for endothelial IRF-1 as a regulator of TNF-α-mediated VCAM-1 induction in endothelial cells was reported before [20,21] . Our data reveal that IRF-1 is expressed in mouse renal endothelial and tubular epithelial cells, and that LPS can induce renal IRF-1 expression in vivo.…”

Section: Discussionmentioning

confidence: 86%

“…In endothelial cells, IRF-1 was recently shown to regulate TNF-α-mediated signaling, which specifically regulated the expression of the adhesion molecule VCAM-1 [20,21] . Recently, we also showed that RIG-I can control VCAM-1 expression in response to LPS challenge [13] .…”

Section: Introductionmentioning

confidence: 99%

Endothelial Interferon Regulatory Factor 1 Regulates Lipopolysaccharide-Induced VCAM-1 Expression Independent of NFκB

Yan¹,

Meurs²,

Popa³

et al. 2017

J Innate Immun

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Sepsis is a severe systemic inflammatory response to infection. Endothelial activation and dysfunction play a critical role in the pathophysiology of sepsis and represent an important therapeutic target to reduce sepsis mortality. Interferon regulatory factor 1 (IRF-1) was recently identified as a downstream target of TNF-α-mediated signal transduction in endothelial cells. The aim of this study was to explore the importance of IRF-1 as a regulator of lipopolysaccharide (LPS)-induced endothelial proinflammatory activation. We found that renal IRF-1 was upregulated by LPS in vivo as well as in LPS-stimulated endothelial cells in vitro. Furthermore, we identified intracellular retinoic acid inducible gene-I (RIG-I) as a regulator of LPS-mediated IRF-1 induction. IRF-1 depletion specifically resulted in diminished induction of VCAM-1 in response to LPS, but not of E-selectin or ICAM-1, which was independent of NFκB signaling. When both IRF-1 and the RIG-I adapter protein mitochondrial antiviral signaling (MAVS) were absent, VCAM-1 induction was not additionally inhibited, suggesting that MAVS and IRF-1 reside in the same signaling pathway. Surprisingly, E-selectin and IL-6 induction were no longer inhibited by MAVS knockdown when IRF-1 was also absent, revealing a redundant endothelial activation pathway. In summary, we report an IRF-1-mediated proinflammatory signaling pathway that specifically regulates LPS-mediated VCAM-1 expression, independent of NFκB.

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“…Moreover, IRF1 is required for TNF induction of IFN-b to promote monocyte recruitment (13,14). Recently, systematic screening of antiviral effectors identified human IRF1 as one of six broadly acting effectors to defend against all viruses tested in IFN-dependent and IFN-independent manners (15,16), underscoring the physical relevance of IRF1 in the innate antiviral response.…”

mentioning

confidence: 99%

Zebrafish IRF1 Regulates IFN Antiviral Response through Binding to IFNϕ1 and IFNϕ3 Promoters Downstream of MyD88 Signaling

Feng

Zhang

et al. 2015

The Journal of Immunology

100

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In mammals, type I IFNs (mainly IFN-α/β) are primarily regulated by transcription factors of the IFN regulatory factor (IRF) family. Fish IFNs do not show a one-to-one orthologous relationship with mammalian type I IFN homologues. Using a bacterial one-hybrid reporter screening system and an overexpression approach to explore the molecular mechanism underlying fish IFN induction, we identified zebrafish Danio rerio IRF (DrIRF)1 as a positive regulator of the fish IFN antiviral response. Among 12 zebrafish IRF family genes, DrIRF1 is most abundant in zebrafish immune tissues, including head kidney and spleen; upon virus infection, it is one of most significantly induced genes. Overexpression of DrIRF1 induces the expression of IFN and IFN-stimulated genes, hence protecting epithelioma papulosum cyprini cells against spring viremia of carp virus infection. As a transcription factor with constitutively nuclear retention, DrIRF1 directly binds to the IFN-stimulated regulatory element/IRF-binding element sites of zebrafish IFN promoters, which are dependent on four conserved amino acids of the N-terminal DNA-binding domain helix α3 motif. Mutation of either residue reveals a differential requirement for DrIRF1-mediated activation of zebrafish IFNϕ1 and IFNϕ3 promoters. Notably, C-terminal phosphorylation of DrIRF1 is observed and is not required for in vitro binding of DrIRF1 to fish IFN promoters. Unlike DrIRF3 and DrIRF7, which are responsible for differential expression of zebrafish IFNϕ1 and IFNϕ3 through the retinoic acid–inducible gene I–like receptor pathway, DrIRF1 works in concert with MyD88 to activate zebrafish IFNϕ3 but not IFNϕ1. These results provide insights into the evolving function of IRF1 as a positive IFN regulator.

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Endothelial TNF Receptor 2 Induces IRF1 Transcription Factor-Dependent Interferon-β Autocrine Signaling to Promote Monocyte Recruitment

Cited by 109 publications

References 49 publications

Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages

Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages

Endothelial Interferon Regulatory Factor 1 Regulates Lipopolysaccharide-Induced VCAM-1 Expression Independent of NFκB

Zebrafish IRF1 Regulates IFN Antiviral Response through Binding to IFNϕ1 and IFNϕ3 Promoters Downstream of MyD88 Signaling

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Endothelial TNF Receptor 2 Induces IRF1 Transcription Factor-Dependent Interferon-β Autocrine Signaling to Promote Monocyte Recruitment

Cited by 109 publications

References 49 publications

Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages

Type-I interferon signaling through ISGF3 complex is required for sustained Rip3 activation and necroptosis in macrophages

Endothelial Interferon Regulatory Factor 1 Regulates Lipopolysaccharide-Induced VCAM-1 Expression Independent of NF&#x03BA;B

Zebrafish IRF1 Regulates IFN Antiviral Response through Binding to IFNϕ1 and IFNϕ3 Promoters Downstream of MyD88 Signaling

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Endothelial Interferon Regulatory Factor 1 Regulates Lipopolysaccharide-Induced VCAM-1 Expression Independent of NFκB