Integrative genomic analyses on interferon-λs and their roles in cancer prediction

Yang, Liming; Wei, Ji‐Fu; He, Shaoheng

doi:10.3892/ijmm_00000345

Int J Mol Med

2009

DOI: 10.3892/ijmm_00000345

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Integrative genomic analyses on interferon-λs and their roles in cancer prediction

Liming Yang

Ji‐Fu Wei²,

Shaoheng He³

Abstract: Abstract. Interferon (IFN)-Ïs, including IFN-Ï1, IFN-Ï2, and IFN-Ï3, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. Besides the antiviral activity, IFN-Ïs were reported to inhibit various tumor growths in vitro and in vivo. Herein, we identified IFN-Ï genes from the genome sequences of the human, chimpanzee, macaque, orangutan, mouse, rat and dog, and found that the locations and copy of a specific IFN-Ï varied in different genomes, not just the copy of … Show more

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Cited by 10 publications

References 32 publications

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lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

Yang

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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The macrophage transformation of inflammatory M1 to anti-inflammatory M2 could be promoted by activating PI3K/AKT signaling pathway. In our previous study, it was found that downregulation of lncRNA260 could ameliorate hypoxic cardiomyocyte injury by regulating IL28RA through the activation of PI3K/AKT signaling pathways. It was suggested that lncRNA260 siRNA could promote the macrophages toward M2 polarization by regulating IL28RA. In this study, lncRNA260 siRNA was used to observe its effect on the polarization of murine bone marrow-derived macrophages (BMDM) and investigate its related mechanisms. lncRNA 260 specific siRNA were designed and synthesized which were transfected into murine BMDM with liposomes. The experiment was divided into three groups: Hypoxia group, Hypoxia+lncRNA 260-specific siRNA transfection group, and Normoxia group. The CD206-APC/CD11b-FITC or CD206-FITC/CD107b (Mac-3) double positive proportions were used to compare the M2 polarization proportions in the hypoxia process by using the immunofluorescence staining method. The p-AKT, Arg 1, PI3KCG, IL28RAV1, and IL28RAV2 protein expression changes were observed by using the western blot method. Compared with the Normoxia group, the M2 proportions were significantly decreased in the Hypoxia group ( P < 0.05 ). Compared with the hypoxia group, the M2 proportions were significantly increased in the Hypoxia+lncRNA260 siRNA transfection group ( P < 0.05 ). In the Hypoxia group, the ratios of Arg 1/β-Actin, p-AKT/β-Actin, PI3KCG/β-Actin, and IL28RAV1/β-Actin were significantly lower than those in the Normoxia group ( P < 0.05 ). After transfection with lncRNA260 siRNA, the ratios of Arg1/β-Actin, p-AKT/β-Actin, PI3KCG/β-Actin, and IL28RAV1/β-Actin were significantly higher than those in the Hypoxia group ( P < 0.05 ). Compared with the Normoxia group, the IL28RAV2/β-Actin in the Hypoxia group was significantly increased ( P < 0.05 ). After transfection with lncRNA260 siRNA, the ratio of IL28RAV2/β-Actin was significantly decreased than that in the Hypoxia group ( P < 0.05 ). lncRNA260 siRNA could promote the M2 polarization of the hypoxia macrophages by reducing the IL28RAV2 alternative splicing variant, which might be related to the activation of the JAK-STAT and PI3K/AKT signaling pathways. It will provide a new strategy for the anti-inflammation, antioxidative stress therapy, and cardiac remodeling after AMI.

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lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

Yang

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Type III Interferons, IL-28 and IL-29, Are Increased in Chronic HCV Infection and Induce Myeloid Dendritic Cell-Mediated FoxP3+ Regulatory T Cells

et al. 2012

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Background & AimsHepatitis C virus (HCV) is difficult to eradicate and type III interferons (IFN-λ, composed of IL-28A, IL-28B and IL-29) are novel therapeutic candidates. We hypothesized that IFN-λ have immunomodulatory effects in HCV- infected individuals.Materials and MethodsWe analyzed the expression of IFN-λ and its receptor (composed of IL-10R2 and IFN-λR subunits) in the blood and livers of patients with chronic (c)HCV infection compared to controls (those who cleared HCV by sustained virological response, SVR, and those with liver inflammation of non-viral origin, non-alcoholic steatohepatitis, NASH). We also compared the proliferative capacity of dendritic cells (DCs) obtained from healthy individuals and those with chronic HCV using a mixed leukocyte reaction combined with 3H-Td incorporation. In addition, the composition of the IFN-λ receptor (IFN-λR) on myeloid DCs, plasmacytoid DCs, PBMCs, and T cells was determined by FACS analysis.ResultsWe report that the expression of IFN-λ protein in serum and mRNA in liver is increased in cHCV patients, but not in those with HCV SVR or NASH, compared to controls. Liver level of IFN-λR mirrored the expression of serum IFN-λ and was higher in cHCV, compared to controls and HCV-SVR patients, suggesting that elevation of IFN-λ and IFN-λR are HCV-dependent. We further identified that innate immune cell populations expressed complete IFN-λ receptor. In vitro, recombinant IFN-λ promoted differentiation of monocyte-derived dendritic cells (DCs) into a phenotype with low T cell stimulatory capacity and high PD-L1 expression, which further promoted expansion of existing regulatory T cells. IFN-λ-DCs failed to induce de novo generation of regulatory T cells. The inhibitory capacity of IFN-λ-DCs was counteracted by recombinant IL-12 and by neutralization of the PD-1/PD-L1 system.ConclusionsOur novel findings of the immunomodulatory effect of IFN-λ contribute to the understanding of the anti-inflammatory and/or anti-viral potential of IFN-λ in cHCV.

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Protective effects of IL28RA siRNA on cardiomyocytes in hypoxia/reoxygenation injury

Gong

Yang³

et al. 2017

Anatol J Cardiol

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Objective:We demonstrate the protective effects of the siRNA-mediated inhibition of the interleukin-28 receptor alpha (IL28RA) subunit on cardiomyocytes in hypoxia/reoxygenation (H/R) injury and explore the associated mechanism.Methods:After designing and synthesizing three pairs of siRNA that effectively reduced IL28RA gene expression in vitro (siRNA-6158, siRNA-6160, and siRNA-6162), primary neonatal rat cardiomyocytes were transfected using a liposome transfection method. Six groups were included based on the siRNA that was used and the treatment simulating reperfusion injury: control group, H/R group, H/R+negative control group, H/R+siRNA-6158 group, H/R+siRNA-6160 group, and H/R+siRNA-6162 group. Cell survival and apoptosis rates were measured along with lactate dehydrogenase levels in the cell culture supernatant. Protein levels of IL28RA, phosphatidylinositol 3-kinase, catalytic subunit gamma (PI3KCG), Bcl-2, Bax, and b-actin were also measured.Results:The H/R+siRNA-6158 and H/R+siRNA-6160 groups had significantly higher survival rates and increased PI3KCG-to-b-actin and Bcl-2-to-Bax ratios than the the H/R and H/R+negative control groups (p<0.05). The H/R+siRNA-6158 and H/R+siRNA-6160 groups also exhibited reduced rates of apoptosis and reduced IL28RA-to-b-actin ratios (p<0.05). No significant difference was observed among the H/R+siRNA-6162, H/R, and H/R+negative control groups.Conclusion:IL28RA siRNA-6158 and -6160 were able to protect cardiomyocytes from H/R injury by inhibiting apoptosis. This strategy of inhibiting IL28RA gene expression may reduce reperfusion injury in the treatment of patients with acute myocardial infarction.

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Integrative genomic analyses on interferon-λs and their roles in cancer prediction

Cited by 10 publications

References 32 publications

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

lncRNA260 siRNA Accelerates M2 Macrophage Polarization and Alleviates Oxidative Stress via Inhibiting IL28RA Gene Alternative Splicing

Type III Interferons, IL-28 and IL-29, Are Increased in Chronic HCV Infection and Induce Myeloid Dendritic Cell-Mediated FoxP3+ Regulatory T Cells

Protective effects of IL28RA siRNA on cardiomyocytes in hypoxia/reoxygenation injury

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