scholarly journals Expression of interferon regulatory factor 5 is regulated by the Sp1 transcription factor

2016 ◽  
Vol 14 (3) ◽  
pp. 2815-2822 ◽  
Author(s):  
Jin Shu ◽  
Xiao-Hua Wang ◽  
Lan-Bo Zhou ◽  
Chun-Ming Jiang ◽  
Wei-Xia Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5 ◽  
Sp1 Transcription Factor

scholarly journals Interferon Regulatory Factor 5 (IRF5) Interacts with the Translation Initiation Complex and Promotes mRNA Translation During the Integrated Stress Response to Amino Acid Deprivation

2017 ◽  
Author(s):  
James D. Warner ◽  
Mandi Wiley ◽  
Ying-Y Wu ◽  
Feng Wen ◽  
Michael Kinter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Stress Response ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Initiation Complex ◽  
Cellular Processes ◽  
Interferon Regulatory Factor 5

ABSTRACTInterferon Regulatory Factor 5 (IRF5) plays an important role in limiting pathogenic infection and tumor development. Host protection by IRF5 can occur through a variety of mechanisms including production of type I interferon and cytokines as well as the regulation of cell survival, growth, proliferation, and differentiation. While modulation of these cellular processes is attributed to IRF5 transcription factor function in the nucleus, emerging evidence suggests that IRF5 may also retain non-transcriptional regulatory properties within the cytoplasmic compartment. Consistent with this notion, we report the ability of IRF5 to control gene expression at the level of mRNA translation. Our findings demonstrate that IRF5 interacts with the translation initiation complex in the absence of the m7GTP cap-binding protein, eIF4E. We observed that under nutrient deprivation-induced cell stress, IRF5 promoted mRNA translation of the master integrated stress response (ISR) regulator, Activating Transcription Factor 4 (ATF4). Enhanced ATF4 protein expression correlated with increased levels of downstream target genes including CHOP and GADD34 and was associated with amplification of eIF2α de-phosphorylation and translational de-repression under stress. The novel mechanism we describe broadens our understanding of how IRF5 regulates gene expression and may govern diverse cellular processes in the absence of stimuli that trigger IRF5 nuclear translocation.

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.

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