Interferon Regulatory Factor 1 Regulates both Autophagy and Apoptosis in Splenocytes during Sepsis

OBJECTIVE: Interferon regulatory factor-1 (IRF-1) is a critical regulator of interferon-gamma(IFNgamma)-mediated immune responses. To determine whether IRF-1 is involved in the pathogenesis of thyroiditis in animal models, we evaluated the incidence of iodide-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice lacking IRF-1 as well as IRF-1 +/+ and +/- mice. DESIGN: IRF-1 +/+, +/- and -/- NOD mice at 6 weeks of age were fed water (group 1) or iodide water (group 2) for 8 weeks. METHODS: Thyroids were examined histopathologically and intrathyroidal lymphocytic infiltration was arbitrarily graded. Serum thyroxine (T(4)) and anti-mouse thyroglobulin antibody (anti-mTgAb) levels were measured. Spleen cell population was analyzed by flow cytometry, and IFNgamma and interleukin-10 produced by splenocytes were measured by enzyme-linked immunosorbent assay. RESULTS: In group 1, only 4.3% of NOD mice developed LT. In contrast, 67.6% of mice in group 2 developed the disease. Iodide treatment induced LT in more than 80% of IRF-1 +/+ and +/- mice. However, no IRF-1 -/- mice in group 2 developed LT. There was no difference in both serum anti-mTgAb and T(4) levels among the three IRF-1 genotypes of NOD mice. Numbers of splenic CD8(+) T cells and IFNgamma production by Concanavalin A-stimulated splenocytes were markedly decreased in IRF-1-deficient NOD mice. CONCLUSIONS: IRF-1 is involved in the development of iodide-induced LT in NOD mice.

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Interferon regulatory factor-1 promoter polymorphism and the outcome of hepatitis C virus infection

European Journal of Gastroenterology & Hepatology ◽

10.1097/01.meg.0000224478.89545.76 ◽

2006 ◽

Vol 18 (9) ◽

pp. 991-997 ◽

Cited By ~ 20

Author(s):

Perdita Wietzke-Braun ◽

Adil B. Maouzi ◽

Larissa B. M??nhardt ◽

Heike Bickeb??ller ◽

Giuliano Ramadori ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Infection ◽

Interferon Regulatory Factor ◽

Promoter Polymorphism ◽

Hepatitis C Virus Infection ◽

Regulatory Factor ◽

Interferon Regulatory Factor 1

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Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses

BioMed Research International ◽

10.1155/2018/2739830 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yongxiang Liu ◽

Xiaoxiao Liu ◽

Hongtao Kang ◽

Xiaoliang Hu ◽

Jiasen Liu ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Interferon Regulatory Factor ◽

Feline Calicivirus ◽

Type I ◽

Norwalk Virus ◽

Regulatory Factor ◽

Feline Panleukopenia Virus ◽

Protein Levels ◽

Interferon Regulatory Factor 1

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

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Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system

Molecular and Cellular Biology ◽

10.1128/mcb.14.2.1500-1509.1994 ◽

1994 ◽

Vol 14 (2) ◽

pp. 1500-1509

Author(s):

H Harada ◽

E Takahashi ◽

S Itoh ◽

K Harada ◽

T A Hori ◽

...

Keyword(s):

Gene Network ◽

Interferon Regulatory Factor ◽

Chromosomal Mapping ◽

Human Interferon ◽

Type I ◽

Regulatory Factor ◽

Nf Kappa B ◽

Interferon Regulatory Factor 1 ◽

Two Factors ◽

Dna Binding Factors

Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; the former functions as a transcriptional activator, and the latter represses IRF-1 function by competing for the same cis elements. More recent studies have revealed new roles of the two factors in the regulation of cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities, respectively. In this study, we determined the structures and chromosomal locations of the human IRF-1 and IRF-2 genes and further characterized the promoters of the respective genes. Comparison of exon-intron organization of the two genes revealed a common evolutionary structure, notably within the exons encoding the N-terminal portions of the two factors. We confirmed the chromosomal mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to 4q35.1, using fluorescence in situ hybridization. The 5' regulatory regions of both genes contain highly GC-rich sequences and consensus binding sequences for several known transcription factors, including NF-kappa B. Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRF-2 gene was affected by both transient and stable IRF-1 expression. In addition, one potential IFN-gamma-activated sequence was found within the IRF-1 promoter. Thus, these results may shed light on the complex gene network involved in regulation of the IFN system.

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The Pivotal Role of Signal Regulatory Protein α in Exacerbating Pulmonary Fibrosis Complicated with Bacterial Infection

Journal of Immune Research ◽

10.26420/jimmunres.2021.1039 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yamaguchi R ◽

◽

Sakamoto A ◽

Haraguchi M ◽

Narahara S ◽

...

Keyword(s):

Immune Response ◽

Pulmonary Fibrosis ◽

Bacterial Infection ◽

Signaling Pathway ◽

Regulatory Protein ◽

Interferon Regulatory Factor ◽

Regulatory Factor ◽

Interferon Regulatory Factor 1 ◽

Th1 Immune Response

The pathogenesis of pulmonary fibrosis remains unknown. However, bacterial infections in patients with idiopathic pulmonary fibrosis are a serious complication that exacerbate the disease. Serum levels of Surfactant Protein D (SPD) are known to be elevated in patients with pulmonary fibrosis, but the role of SPD in pulmonary fibrosis complicated with bacterial infection is unknown. Lipopolysaccharide upregulates Interleukin (IL)-12p40 expression and IL-12p40 promotes Interferon Gamma (IFNγ) production to induce the T helper cell 1 (Th1) immune response via Signal Transducers and Activators of Transcription 4 (STAT4) signaling. A lack of IFNγ shifts the immune response from Th1 to Th2. IL-4 is a profibrotic Th2 cytokine that activates fibroblasts. Granulocyte-macrophage colony-stimulating factor induced by IL-1 and TNFα during the Th1 immune response upregulates Signal Regulatory Protein α (SIRPα) expression. Interferon Regulatory Factor 1 (IRF1) functions as the promoter activator of IL-12p40 after stimulation with LPS. SPD is a ligand for SIRPα, and SPD/SIRPα ligation activates the Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Related Kinase (ERK) signal cascade; ERK downregulates Interferon Regulatory Factor 1 (IRF1) expression. Consequently, the SPD/SIRPα signaling pathway decreases IL-12p40 production in human macrophages after exposure to LPS. IL-12p40 is a key immunoregulatory factor in bacterial infection that promotes production of IFNγ by T lymphocytes. Pulmonary fibroblasts are activated by IL-4/IL-4R ligation. IFNγ induces IRF1 via STAT1 signaling, and IRF1 acts as the promoter repressor of IL-4 to attenuate its production. IFNγ also inhibits IL-4R expression. A reduction in IFNγ induced by IL-12p40 deficiency via the SPD/SIRPα signaling pathway enhances IL-4 and IL-4R expression to augment the activity of fibroblasts. This finding indicates that pulmonary fibrosis is exacerbated by SPD/SIRPα signaling during bacterial infection.

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