Background/Aims: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-β) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. Methods: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells. Results: YY1 was shown to interact with STAT1 in the absence of viral infection. Following viral infection, YY1 protein expression levels were decreased. YY1 knockdown led to a considerable downregulation of phosphorylated (p) TBK1 and pIRF3 expressions, while YY1 overexpression significantly upregulated pTBK1 and pIRF3 expression levels and promoted virus-induced IFN-β production. Additionally, YY1 knockdown led to a significant upregulation of pSTAT1, pSTAT2 and antiviral interferon-stimulated genes, and inhibited viral replication. Conclusion: We demonstrated here that YY1 interacts with STAT1 and dynamically regulates the induction of IFN-1 production and activation of IFN-1 signaling in different stages during viral infection.
Background and PurposeSubarachnoid hemorrhage (SAH)‐induced cerebral vasospasm and early brain injury is a fatal clinical syndrome. Cerebral vasospasm and early brain injury are associated with inflammatory response and oxidative stress. Whether curcumin, which plays important roles to regulate inflammatory cytokines and inhibit oxidative stress, inhibits SAH‐induced inflammation and oxidative stress are largely unknown.MethodsAdult male rats underwent autologous blood injection into prechiasmatic cistern to induce SAH. Curcumin (150 mg/kg) was administered at 0.5, 24 and 48 hr post‐SAH. Mortality calculation and neurological outcomes as well as morphological vasospasm of anterior cerebral artery were studied. Superoxide dismutase, lipid peroxidation, and inflammatory cytokines (MCP‐1 and TNF‐α) expression in prefrontal region were quantified. Furthermore, p65 and phosphor‐p65 were quantitatively analyzed.ResultsCurcumin remarkedly reduced mortality and ameliorated neurological deficits after SAH induction (p < .05); morphological results showed that cerebral vasospasm in curcumin‐treated group was mitigated (p < .05). SAH‐induced MCP‐1 and TNF‐α overexpression were inhibited in curcumin‐treated group (p < .05). Importantly, phosphor‐p65 was significantly inhibited after curcumin treatment (p < .05).ConclusionsCurcumin can inhibit SAH‐induced inflammatory response via restricting NF‐κB activation to alleviate cerebral vasospasm and early brain injury.
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