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Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs) are novel regulators of immunity, there has been no systematic attempt to identify and characterize the lncRNAs whose expression is changed following the induction of the innate immune response. To address this issue, we have employed next-generation sequencing data to determine the changes in the lncRNA profile in four human (monocytes, macrophages, epithelium, and chondrocytes) and four mouse cell types (RAW 264.7 macrophages, bone marrow-derived macrophages, peritoneal macrophages, and splenic dendritic cells) following exposure to the pro-inflammatory mediators, lipopolysaccharides (LPS), or interleukin-1β. We show differential expression of 204 human and 210 mouse lncRNAs, with positional analysis demonstrating correlation with immune-related genes. These lncRNAs are predominantly cell-type specific, composed of large regions of repeat sequences, and show poor evolutionary conservation. Comparison within the human and mouse sequences showed less than 1% sequence conservation, although we identified multiple conserved motifs. Of the 204 human lncRNAs, 21 overlapped with syntenic mouse lncRNAs, of which five were differentially expressed in both species. Among these syntenic lncRNA was (antisense), which was induced in multiple cell types and shown to regulate the production of the pro-inflammatory mediator interleukin-6 in both human and mouse cells. In summary, we have identified and characterized those lncRNAs that are differentially expressed following activation of the human and mouse innate immune responses and believe that these catalogs will provide the foundation for the future analysis of the role of lncRNAs in immune and inflammatory responses.
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http://dx.doi.org/10.3389/fimmu.2017.01038 | DOI Listing |
Mol Ther Methods Clin Dev
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Eisai Co., Ltd., Tsukuba Research Laboratories, 5-1-3, Tokodai, Tsukuba, Ibaraki 300-2635, Japan.
Liver-humanized chimeric mice (PXB-mice) are widely utilized for predicting human pharmacokinetics (PK) and as human disease models. However, residual metabolic activity of mouse hepatocytes in chimeric mice can interfere with accurate human PK estimation. Lipid nanoparticle (LNP)-formulated small interfering RNA (siRNA) treatment makes it possible to eliminate the shortcomings of chimeras and create new models.
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Shanghai Vitalgen BioPharma Co., Ltd., Shanghai 201210, China.
Bietti crystalline dystrophy (BCD) is an autosomal recessive disorder caused by loss-of-function mutations in the gene, characterized by crystal-like lipid deposits in the retina, progressive photoreceptor loss, and retinal pigment epithelium (RPE) deterioration. Currently, there are no approved treatments for BCD. VGR-R01, an investigational gene therapy, uses subretinal administration of recombinant adeno-associated virus type 8 (AAV8) vector to deliver the human CYP4V2 gene.
View Article and Find Full Text PDFRegen Biomater
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Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
Reconstructing bone defects remains a significant challenge in clinical practice, driving the urgent need for advanced artificial grafts that simultaneously promote vascularization and osteogenesis. Addressing the critical trade-off between achieving high porosity/strength and effective bioactivity at safe ion doses, we incorporated strontium (Sr) into β-tricalcium phosphate (β-TCP) scaffolds with a triply periodic minimal surface (TPMS) structure using digital light processing (DLP)-based three-dimensional (3D) printing. Systematically screening Sr concentrations (0-10 mol%), we identified 10 mol% as optimal, leveraging the synergy between the biomimetic TPMS architecture, providing exceptional mechanical strength (up to 1.
View Article and Find Full Text PDFFront Immunol
September 2025
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
NSG-SGM3 humanized mouse models are well-suited for studying human immune physiology but are technically challenging and expensive. We previously characterized a simplified NSG-SGM3 mouse, engrafted with human donor CD34 hematopoietic stem cells without receiving prior bone marrow ablation or human secondary lymphoid tissue implantation, that still retains human mast cell- and basophil-dependent passive anaphylaxis responses. Its capacities for human antibody production and human B cell maturation, however, remain unknown.
View Article and Find Full Text PDFRSC Med Chem
August 2025
Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798-7348, United States of America.
A strategy for targeting tumor-associated hypoxia utilizes reductase enzyme-mediated cleavage to convert biologically inert prodrugs to their corresponding biologically active parent therapeutic agents selectively in areas of pronounced hypoxia. Small-molecule inhibitors of tubulin polymerization represent unique therapeutic agents for this approach, with the most promising functioning as both antiproliferative agents (cytotoxins) and as vascular disrupting agents (VDAs). VDAs selectively and effectively disrupt tumor-associated microvessels, which are typically fragile and chaotic in nature.
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