Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection

Kędzierski, Łukasz; Linossi, Edmond M.; Kolesnik, Tatiana B.; Day, E. Bridie; Bird, Nicola L.; Kile, Benjamin T.; Belz, Gabrielle T.; Metcalf, Donald; Nicola, Nicos A.; Kedzierska, Katherine; Nicholson, Sandra E.

doi:10.1371/journal.ppat.1004134

Cited by 56 publications

(77 citation statements)

References 63 publications

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“…SOCS4 belongs to the SOCS family that is composed of eight members, including cytokine-inducible Src-homology 2 protein (CIS), as well as SOCS1 to 7 (22,23). These proteins are known to be cytokine-inducible negative regulators of cytokine signaling, as well as key regulators of innate and adaptive immunity (24). Galic et al (25) also reported that the SOCS family proteins serve an critical role in mediating inflammatory responses in immune cells and metabolic organs.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑let‑7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1/signal transducer and activator of transcription 3 pathway

Zhang

Jiang

et al. 2018

Exp Ther Med

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Abstract. The present study aimed to explore the microRNA-let-7e (miR-let-7e) expression in allergic rhinitis (AR), and to investigate the underlying molecular mechanisms. miR-let-7e expression in the nasal mucosa of mice and patients with AR were detected. The expression levels of three inflammatory factors, including histamine, immunoglobulin E and tumor necrosis factor-α (TNF-α), in the blood of AR mice and in interleukin (IL)-13-stimulated nasal epithelial cells (NECs) were also measured. Furthermore, the target gene of miR-let-7e was predicted and validated using a luciferase reporter assay. The expression levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) were detected. The results demonstrated that miR-let-7e was downregulated in patients and mice with AR compared with the controls. In addition, the expression levels of inflammatory factors were higher in the blood of mice with AR compared with the control group, while miR-let-7e overexpression inhibited these levels in AR mice and IL-13-stimulated NECs. Furthermore, suppressor of cytokine signaling 4 (SOCS4) was revealed as a potential target gene of miR-let-7e and was negatively regulated by miR-let-7e. Overexpression of SOCS4 abrogated the anti-inflammatory activity of miR-let-7e overexpression. Finally, miR-let-7e overexpression activated the JAK1/STAT3 signaling pathway. In conclusion, miR-let-7e may serve an important role in the progression and development of AR, while overexpression of miR-let-7e had an anti-inflammatory effect by targeting SOCS4, which may be achieved by activation of the JAK1/STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑let‑7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1/signal transducer and activator of transcription 3 pathway

Zhang

Jiang

et al. 2018

Exp Ther Med

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“…Airway epithelial cells are the primary targets for influenza virus infection, and upon infection, they produce important levels of inflammatory cytokines (40). Interestingly, the treatment of human bronchial epithelial cells with ILG significantly reduced the expression of the inflammatory cytokines induced after influenza virus infection.…”

Section: Discussionmentioning

confidence: 99%

The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

Traboulsi

Cloutier

Kumaraswamy

et al. 2015

Antimicrob Agents Chemother

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The host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC 50 ] ‫؍‬ 24.7 M). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8 ؉ effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/ kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

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“…Defect of control of cytokine synthesis and activity (possible development of the "cytokine storm") [27,36] …”

Section: Socs4mentioning

confidence: 99%

“…The risk of severe influenza infection control of the activation of proinflammatory cytokines synthesis [36]. The interest in the genetic control of these processes is natural.…”

Section: Complex Of Se -Dependent Enzymesmentioning

confidence: 99%

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Mutations in human genes that increase the risk for severe influenza infection

Киселев

Komissarov

Коншина

et al. 2015

Microbiology Independent Research Journal (MIR Journal)

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Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection

Cited by 56 publications

References 63 publications

MicroRNA‑let‑7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1/signal transducer and activator of transcription 3 pathway

MicroRNA‑let‑7e regulates the progression and development of allergic rhinitis by targeting suppressor of cytokine signaling 4 and activating Janus kinase 1/signal transducer and activator of transcription 3 pathway

The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

Mutations in human genes that increase the risk for severe influenza infection

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