scholarly journals Retraction for Korczeniewska and Barnes, “The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability”

2017 ◽  
Vol 37 (24) ◽  
Author(s):  
Justyna Korczeniewska ◽  
Betsy J. Barnes
Keyword(s):  
Protein Stability ◽  
Interferon Regulatory Factor ◽  
Cop9 Signalosome ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

scholarly journals The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability

2012 ◽  
Vol 33 (6) ◽  
pp. 1124-1138 ◽  
Author(s):  
Justyna Korczeniewska ◽  
Betsy J. Barnes
Keyword(s):  
Protein Stability ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Death Receptor ◽  
Interferon Regulatory Factor ◽  
Cop9 Signalosome ◽  
Small Interfering Rnas ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5 ◽  
Enhanced Degradation

The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response toward extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single internal deletion from amino acids 455 to 466 (Δ455-466) was found to significantly reduce IRF5 protein stability. CSN subunit 3 (CSN3) was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs resulted in enhanced degradation. Degradation was further augmented by knockdown of CSN1 and CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor MG132 prevented IRF5 degradation, supporting the idea that its stability is regulated by the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction. This study defines CSN to be a new interacting partner of IRF5 that controls its stability.

scholarly journals Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates Interferon Regulatory Factor 5 Protein Stability

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Justyna Korczeniewska ◽  
Betsy J. Barnes
Keyword(s):  
Protein Stability ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Death Receptor ◽  
Interferon Regulatory Factor ◽  
Cop9 Signalosome ◽  
Small Interfering Rnas ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5 ◽  
Enhanced Degradation

ABSTRACT The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability. The constitutive CSN/IRF5 interaction was identified using proteomics and confirmed by endogenous immunoprecipitations. The CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single internal deletion (Δ455-466) was found to significantly reduce IRF5 protein stability. CSN3 was identified as a direct interacting partner of IRF5, and knockdown of this subunit with small interfering RNAs (siRNAs) resulted in enhanced degradation. Degradation was further augmented by knockdown of CSN1 and CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor MG132 prevented IRF5 degradation, supporting that its stability is regulated by the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death receptor ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction. This study defines the CSN as a new interacting partner of IRF5 that controls its stability.

scholarly journals Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis

2007 ◽  
Vol 56 (7) ◽  
pp. 2202-2210 ◽  
Author(s):  
Snaevar Sigurdsson ◽  
Leonid Padyukov ◽  
Fina A. S. Kurreeman ◽  
Ulrika Liljedahl ◽  
Ann-Christin Wiman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Promoter Region ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

Associations between interferon regulatory factor 5 polymorphisms and rheumatoid arthritis: a meta-analysis

2012 ◽  
Vol 40 (2) ◽  
pp. 1791-1799 ◽  
Author(s):  
Young Ho Lee ◽  
Sang-Cheol Bae ◽  
Sung Jae Choi ◽  
Jong Dae Ji ◽  
Gwan Gyu Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

scholarly journals Interferon Regulatory Factor 5 Mediates Lipopolysaccharide-Induced Neuroinflammation

2020 ◽  
Vol 11 ◽  
Author(s):  
Ziqi Fan ◽  
Shuai Zhao ◽  
Yueli Zhu ◽  
Zheyu Li ◽  
Zhirong Liu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Interferon Regulatory Factor ◽  
Microglial Cells ◽  
Regulatory Factor ◽  
Down Regulation ◽  
Interferon Regulatory Factor 5 ◽  
Bv2 Microglial Cells ◽  
Lps Treatment ◽  
Pro Inflammatory Cytokines

BackgroundActivated microglia play a vital role in neuroinflammation in the central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in the periphery, the role of which in the CNS remains elusive.MethodsLipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immunofluorescence and Western blot.ResultsLPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b-positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which were comparable to control group at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling.ConclusionsIRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia.

scholarly journals Interferon Regulatory Factor‐5 in Resident Macrophage Promotes Polycystic Kidney Disease

Kidney360 ◽  
2020 ◽  
Vol 1 (3) ◽  
pp. 179-190
Author(s):  
Kurt A. Zimmerman ◽  
Jifeng Huang ◽  
Lan He ◽  
Dustin Z. Revell ◽  
Zhang Li ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Cytokine Production ◽  
Interferon Regulatory Factor ◽  
Cystic Disease ◽  
Regulatory Factor ◽  
Polycystic Kidney ◽  
Qrt Pcr ◽  
Interferon Regulatory Factor 5 ◽  
Stat3 Phosphorylation

BackgroundAutosomal dominant polycystic kidney disease is caused by genetic mutations in PKD1 or PKD2. Macrophages and their associated inflammatory cytokines promote cyst progression; however, transcription factors within macrophages that control cytokine production and cystic disease are unknown.MethodsIn these studies, we used conditional Pkd1 mice to test the hypothesis that macrophage-localized interferon regulatory factor-5 (IRF5), a transcription factor associated with production of cyst-promoting cytokines (TNFα, IL-6), is required for accelerated cyst progression in a unilateral nephrectomy (1K) model. Analyses of quantitative real-time PCR (qRT-PCR) and flow-cytometry data 3 weeks post nephrectomy, a time point before the onset of severe cystogenesis, indicate an accumulation of inflammatory infiltrating and resident macrophages in 1K Pkd1 mice compared with controls. qRT-PCR data from FACS cells at this time demonstrate that macrophages from 1K Pkd1 mice have increased expression of Irf5 compared with controls. To determine the importance of macrophage-localized Irf5 in cyst progression, we injected scrambled or IRF5 antisense oligonucleotide (ASO) in 1K Pkd1 mice and analyzed the effect on macrophage numbers, cytokine production, and renal cystogenesis 6 weeks post nephrectomy.ResultsAnalyses of qRT-PCR and IRF5 ASO treatmentsignificantly reduced macrophage numbers, Irf5 expression in resident—but not infiltrating—macrophages, and the severity of cystic disease. In addition, IRF5 ASO treatment in 1K Pkd1 mice reduced Il6 expression in resident macrophages, which was correlated with reduced STAT3 phosphorylation and downstream p-STAT3 target gene expression.ConclusionsThese data suggest that Irf5 promotes inflammatory cytokine production in resident macrophages resulting in accelerated cystogenesis.

Zinc Deficiency Activates the IL-23/Th17 Axis to Aggravate Experimental Colitis in Mice

2019 ◽  
Vol 14 (6) ◽  
pp. 856-866 ◽  
Author(s):  
Yasuki Higashimura ◽  
Tomohisa Takagi ◽  
Yuji Naito ◽  
Kazuhiko Uchiyama ◽  
Katsura Mizushima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lamina Propria ◽  
Zinc Deficiency ◽  
Mononuclear Cells ◽  
Interferon Regulatory Factor ◽  
Nuclear Accumulation ◽  
Regulatory Factor ◽  
Colonic Inflammation ◽  
Interferon Regulatory Factor 5 ◽  
Lamina Propria Mononuclear Cells

Abstract Background and Aims Patients with inflammatory bowel disease [IBD], especially Crohn’s disease, often develop zinc deficiency. However, the precise mechanisms by which zinc deficiency affects IBD pathology, particularly intestinal macrophage function, remain unclear. We studied the effects of zinc deficiency on the development and progression of colitis in mice. Methods To induce colitis, mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Rag1−/− mice were then given injections of naïve CD4+CD62L+ T cells. The respective degrees of mucosal injury of mice that had received a zinc chelator (TPEN; N,N,N′,N′-tetrakis [2-pyridylmethyl]ethylenediamine) and of control mice were subsequently compared. Colonic lamina propria mononuclear cells were isolated by enzymatic digestion and were examined using flow cytometry. To generate mouse bone marrow-derived macrophages [BMDMs], bone marrow cells were stimulated with mouse macrophage-colony stimulating factor. Results Zinc deficiency aggravates colonic inflammation through the activation of type 17 helper T [Th17] cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory [M1] macrophages in colonic lamina propria mononuclear cells obtained from inflamed colon. Interferon-γ plus lipopolysaccharide-mediated M1 skewing alters the expression of zinc transporters in BMDMs and thereby decreases the intracellular free zinc. TPEN treatment mimicking the effects of the M1 skewing up-regulates IL-23p19 expression, which is strongly related to Th17 development. Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is closely involved in IL-23p19 induction in zinc-deficient macrophages. Conclusions Zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis. This activation is controlled by subcellular distribution of interferon-regulatory factor 5.

Interferon Regulatory Factor-5 (irf5) contrôle le métabolisme cellulaire des macrophages tissulaires dans le diabète de type 2

2017 ◽  
Vol 43 (2) ◽  
pp. A28-A29
Author(s):  
Fawaz Alzaid ◽  
Raphaelle Ballaire ◽  
Valerie Paradis ◽  
Qifeng Zhang ◽  
Fabienne Foufelle ◽  
...  
Keyword(s):  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Diabète De Type 2 ◽  
Interferon Regulatory Factor 5
Sign in / Sign up

Export Citation Format

Share Document