Interleukin-27-adipose-derived mesenchymal stromal cell-based gene therapy attenuates inflammation in lipopolysaccharide-induced acute respiratory distress syndrome
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PROVIDER: PRJNA1240220 | ENA |
REPOSITORIES: ENA
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Project description:Acute respiratory distress syndrome (ARDS) is a lung inflammatory condition associated with the accumulation of fluid edema and cell infiltrates into the alveolar space along with the dysregulation in the immune response. Current therapeutics are limited to palliative care, i.e., mechanical ventilators, thus highlighting the need of developing targeted therapeutic for ARDS. Interleukin-27 (IL-27) is a multifunctional cytokine with the capability for immune modulation. Our interest lies in exploring the properties of IL-27, particularly as an anti-inflammatory cytokine that functions as an antagonist of IL-6 signaling, as an inducer of anti-viral genes, as a promoter of tissue repair, and as a regulator of both the innate and adaptive immune responses, possessing promising potential as a therapeutic for ARDS. To overcome the challenge of repeated administration due to the short half-life of cytokines, we utilized a cell-based gene therapy approach. IL-27-expressing plasmid was transfected into adipose mesenchymal stromal cells (ASC) that serve as the gene therapy carriers. For in vitro studies, we treated mono- and co-culture lung lipopolysaccharide (LPS)-induced lung epithelial and monocytes/macrophages cell line with IL-27-expressing ASC (IL-27) conditioned media (CM) to determine the effects on pro-inflammatory gene expression. For in vivo studies, male C57BL/6 mice was intratracheally injected with LPS (5mg/kg) and treated either PBS, ASC, or IL-27 ASC (5 x 105 cells/mouse) after 24h of LPS instillation. Measurements of gene expression, histopathological changes, cell infiltrations, and protein content in the bronchoalveolar lavage fluid and RNA-seq analysis were performed for the in vivo studies. Results indicated that IL-27ASC CM were able to reduce pro-inflammatory gene expression of lung epithelial and macrophages cultured in both mono- and co-culture systems. Additionally, IL-27 ASC were able to reduce pro-inflammatory markers, decrease cell infiltration into the lungs, promote genes and immune cells involved in tissue repair, and rebalance innate and adaptive immunity in an LPS-induced in vivo model. Collectively, our in vitro and in vivo results showed promising potential for IL-27 cell-based gene therapy as a treatment for ARDS.
2025-08-25 | GSE292564 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE16180: Bone-marrow derived macrophages response to the Whipple's disease agent, Tropheryma whipplei GSE20207: Wild-type bone-marrow derived macrophages response to Escherichia coli lipopolysaccharide (LPS) GSE20208: Interleukin-16-knock-out bone-marrow derived macrophages response to Escherichia coli lipopolysaccharide (LPS) GSE20209: Interleukin-16-knock-out bone-marrow derived macrophages response to the Whipple's disease agent, Tropheryma whipplei Refer to individual Series
2010-11-08 | E-GEOD-20210 | biostudies-arrayexpress
Project description:Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo, suggest that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. We reported that IFNs and IL-27 activate JAK-STAT signaling and induce shared pro-inflammatory and antiviral pathways in monocyte-derived macrophages (MDMs), leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs). Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response.
2024-04-15 | GSE262963 | GEO
Project description:Acute respiratory distress syndrome (ARDS) remains a common and devastating syndrome. CircRNAs are crucial in a variety of diseases and can provide new potential diagnostic and therapeutic targets for disease. The development of circular RNA (circRNA) microarray has facilitated the study of the role of circRNAs in regulating gene expression. This research was designed to explore the expression profile of circRNAs in lung tissues from rats with lipopolysaccharide-induced ARDS. Our findings indicate that the expression profiles of circRNAs has changed in ARDS as compared with normal rat lung tissue, and may provide novel insight into the molecular mechanism underlying the disease and potential novel diagnostic or therapeutic targets for ARDS.
2017-08-12 | GSE102523 | GEO
Project description:Interleukin (IL)-27 is a key immunosuppressive cytokine that counters T helper 17 (Th17) cell-mediated pathology. To identify mechanisms by which IL-27 might exert its immunosuppressive effect, we analyzed genes in T cells rapidly induced by IL-27. We found that IL-27 priming of naïve T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)1-dependent manner. When co-cultured with naïve CD4+ T cells, IL-27-primed T cells inhibited the differentiation of Th17 cells in trans through a PD-1-PD-L1 interaction. In vivo, co-administration of naïve TCR transgenic T cells (2D2 T cells) with IL-27-primed T cells expressing PD-L1 inhibited the development of Th17 cells and protected from severe autoimmune encephalomyelitis. Thus, these data identify a suppressive activity of IL-27, by which CD4+ T cells can restrict differentiation of Th17 cells in trans.
2012-07-01 | GSE38375 | GEO
Project description:Interleukin (IL)-27 is a key immunosuppressive cytokine that counters T helper 17 (Th17) cell-mediated pathology. To identify mechanisms by which IL-27 might exert its immunosuppressive effect, we analyzed genes in T cells rapidly induced by IL-27. We found that IL-27 priming of naïve T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)1-dependent manner. When co-cultured with naïve CD4+ T cells, IL-27-primed T cells inhibited the differentiation of Th17 cells in trans through a PD-1-PD-L1 interaction. In vivo, co-administration of naïve TCR transgenic T cells (2D2 T cells) with IL-27-primed T cells expressing PD-L1 inhibited the development of Th17 cells and protected from severe autoimmune encephalomyelitis. Thus, these data identify a suppressive activity of IL-27, by which CD4+ T cells can restrict differentiation of Th17 cells in trans. The roles of IL-6 and IL-27 in naïve CD4+ T cells was investigated by comparing global gene expression by Affymetrix Mouse Genome 430 2.0 Arrays. The functional outcome of STAT proteins was further evaluated by profiling gene expression changes between WT and STAT-deficient T cells in naïve CD4+ T cells with specific stimulation. All condition were done in biological triplicate.
2012-06-30 | E-GEOD-38375 | biostudies-arrayexpress
Project description:We have employed whole genome microarray expression profiling to identify differently expressed genes following stimulation of interleukin-16-knock-out bone-marrow derived macrophages with Escherichia coli lipopolysaccharide (LPS). Macrophages were stimulated with LPS (100 ng/ml) for 6 hours and a signature was identified that distinguished between infected and control samples. Expression of several genes from this signature was quantified in the same RNA samples by real-time PCR, confirming the predicted macrophage response pattern.
2010-10-08 | GSE20208 | GEO
Project description:We have employed whole genome microarray expression profiling to identify differently expressed genes following stimulation of interleukin-16-knock-out bone-marrow derived macrophages with Escherichia coli lipopolysaccharide (LPS). Macrophages were stimulated with LPS (100 ng/ml) for 6 hours and a signature was identified that distinguished between infected and control samples. Expression of several genes from this signature was quantified in the same RNA samples by real-time PCR, confirming the predicted macrophage response pattern. Gene expression in macrophages was measured at 6 hours after stimulation Three independent experiments were performed.
2010-10-08 | E-GEOD-20208 | biostudies-arrayexpress
Project description:Transcriptional profile of human monocyte-derived macrophages stimulated with Interleukin 27
| PRJNA1095003 | ENA
Project description:Interleukin-27 (IL-27) has shown promise in halting tumor growth and mediating tumor regression in several models, including prostate cancer. We describe our findings on the effects of IL-27 on the gene expression changes of TC2R prostate adenocarcinoma cells. We utilized RNAseq to assess profile differences between empty vector control, vector delivering IL-27 modified at its C-terminus with a non-specific peptide, and IL-27 modified at the C-terminus with a peptide targeting the IL-6-Rα. The targeted IL-27 had higher bioactivity and activity in vivo in a recent study by our group, but the mechanisms underlying this effect had not been characterized in detail at the gene expression level on tumor cells. In the present work, we sought to examine potential mechanisms for targeted IL-27 enhanced activity directly on tumor cells. The targeted IL-27 appeared to modulate several changes that would be consistent with an anti-tumor effect, including upregulation in the Interferon (IFN) and Interferon regulatory factor (IRF), oxidative phosphorylation, Janus kinase/Signal transducers and activators of transcription (JAK/STAT), and eukaryotic initiation factor 2 (EIF2) signaling. Of these signaling changes predicted by ingenuity pathway analyses (IPA), the novel form also with the highest significance (-log(Benjamini–Hochberg (B-H))p-value) was the EIF2 signaling upregulation. We validated this predicted change by assaying for eukaryotic initiation factor 2 alpha (eIF2α), or phosphorylated eIF2α (p-eIF2α), and caspase-3 levels. We detected an increase in the phosphorylated form of eIF2α and in the cleaved caspase-3 fraction, indicating that the EIF2 signaling pathway was upregulated in these prostate tumor cells following targeted IL-27 gene delivery. This approach of targeting cytokines to enhance their activity against cancer cells is a novel approach to help augment IL-27′s bioactivity and efficacy against prostate tumors and could be extended to other conditions where it could help interfere with the EIF2α pathway and promote caspase-3 activation.
2024-08-28 | GSE248482 | GEO