Apolipoprotein A-I mimetic peptide L37pA attenuates IFNα-induced inflamation and promotes antiviral activity
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ABSTRACT:
PROVIDER: PRJNA682989 | ENA |
REPOSITORIES: ENA
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Project description:Apolipoprotein A-I mimetic peptides are amphipathic alpha helix peptides that display similar functions to apolipoprotein A-I, and preclinical studies have evaluated . In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.
2020-12-08 | GSE162764 | GEO
Project description:Apolipoprotein A-I mimetic peptides are amphipathic alpha-helix peptides that display similar functions to apolipoprotein A-I. Preclinical and clinical studies have demonstrated the safety and efficacy of apolipoprotein A-I mimetic peptides in multiple indications associated with inflammatory processes. In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.
2021-09-09 | PXD023281 | Pride
Project description:The apolipoprotein A-I (apoA-I) mimetic peptide 4F displays prominent anti-inflammatory properties, including the ability to reduce vascular macrophage content. Macrophages are a heterogenous group of cells, represented by two principal phenotypes, the classically activated M1 macrophage and an alternatively activated M2 phenotype. We recently reported that 4F favors the differentiation of human monocytes to an anti-inflammatory phenotype similar to that displayed by M2 macrophages. In the current study, microarray analysis of gene expression in monocyte-derived macrophages (MDMs) was carried out to identify inflammatory pathways modulated by 4F treatment. ApoA-I treatment of MDMs served as a control. Transcriptional profiling revealed that 4F and apoA-I modulated expression of 113 and 135 genes that regulate inflammatory responses, respectively. Cluster heat maps revealed that 4F and apoA-I induced similar changes in expression for 69 common genes. Modulation of other gene products, including STAT1 and PPARG, were unique for 4F treatment. Besides modulating inflammatory responses, 4F was found to alter gene expression in cell-to-cell signaling, cell growth/proliferation, lipid metabolism and cardiovascular system development. These data suggest that the protective effects of 4F in a number of disease states may be due to underlying changes in monocyte/macrophage gene expression. 16 samples analyzed (four 4F+LPS, four 4F, four Controls+LPS, four Controls).
2012-09-30 | E-GEOD-36933 | biostudies-arrayexpress
Project description:The apolipoprotein A-I (apoA-I) mimetic peptide 4F displays prominent anti-inflammatory properties, including the ability to reduce vascular macrophage content. Macrophages are a heterogenous group of cells, represented by two principal phenotypes, the classically activated M1 macrophage and an alternatively activated M2 phenotype. We recently reported that 4F favors the differentiation of human monocytes to an anti-inflammatory phenotype similar to that displayed by M2 macrophages. In the current study, microarray analysis of gene expression in monocyte-derived macrophages (MDMs) was carried out to identify inflammatory pathways modulated by 4F treatment. ApoA-I treatment of MDMs served as a control. Transcriptional profiling revealed that 4F and apoA-I modulated expression of 113 and 135 genes that regulate inflammatory responses, respectively. Cluster heat maps revealed that 4F and apoA-I induced similar changes in expression for 69 common genes. Modulation of other gene products, including STAT1 and PPARG, were unique for 4F treatment. Besides modulating inflammatory responses, 4F was found to alter gene expression in cell-to-cell signaling, cell growth/proliferation, lipid metabolism and cardiovascular system development. These data suggest that the protective effects of 4F in a number of disease states may be due to underlying changes in monocyte/macrophage gene expression.
2012-09-30 | GSE36933 | GEO
Project description: Not available
| S-EPMC7940203 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE17299: Direct effects of IFNα on human CD8 T cells_without any other concomitant signals GSE17301: The effect of IFNα on human CD8 T cells_with other concomitant signals Refer to individual Series
2010-07-23 | E-GEOD-17302 | biostudies-arrayexpress
Project description:The cause of systemic lupus erythematosus (SLE) is unknown. Interferonα (IFNα) has been suggested as a causative agent of SLE, however, it is not proven, and to what extent and how IFNα contributes to the disease is unknown. We here directly studied the contribution of IFNα to SLE by generating inducible IFNα transgenic mice which showed that conditional up-regulation of IFNα induced a typical manifestation of SLE including serum immune complex (IC), autoantibody against double stranded DNA (anti-dsDNA Ab) and the organ manifestations classical to SLE such as IC-deposited glomerulonephritis, classical splenic onion-skin lesion, and alopecia, epidermal liquefaction, positive lupus-band test of the skin. In the spleen of mice, activated effector CD4 T cells, interferonγ-producing CD8 T cells, B220+CD86+ cells and CD11c+CD86+ cells were increased, and the T cells produced increased amounts of IL-4, IL-6, IL-17 and IFNγ and decreased IL-2. In particular, activated CD3+CD4-CD8- double-negative T (DNT) cells positive for TCRαβ, B220, CD1d-teteramer, PD-1 and Helios, which produced increased amounts of IFNγ, IL-4, IL-17 and TNFα, were significantly expanded. They infiltrated into kidney and induced de novo glomerulonephritis and alopecia when transferred into naïve recipients. Thus, conditional up-regulation of IFNα is sufficient to induce SLE, and the DNT cells as expanded by IFNα are directly responsible for the organ manifestations such as lupus skin disease or nephritis.
2018-12-10 | GSE123549 | GEO
Project description:In order to identify IFNα-induced host factor(s) that might inhibit replication of unadapted chimeric SIV/HIV-1 viruses (SHIVs), we measured IFNα-induced gene expression in immortalized pig-tailed macaque (Ptm) CD4+ lymphocytes. Triplicate cultures of Ptm lymphocytes were left untreated or treated with 1000 U/ml of IFNα. Twenty-four hours later, RNA was isolated, and RNA-seq libraries were prepared for sequencing. A total of 198 genes were found to be significantly differentially expressed (|logFC| ≥ 0.585 & FDR 5%) upon IFNα treatment. 147/198 genes were found to be significantly upregulated and 51/198 genes were found to be significantly downregulated regulated upon IFNα treatment.
2019-06-24 | GSE126594 | GEO
Project description:We designed and demonstrated a synthetic strategy to derive mimetic Vγ9Vδ2 T cells endowed with NKRs from iPSCs. We used microarrays to compare mRNA expression profiles of such iPSC-derived mimetic Vγ9Vδ2 T cells with other peripheral blood lymphocytes.
2019-05-31 | GSE126035 | GEO
Project description: Not available
| S-EPMC5009400 | biostudies-literature