Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA94503 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, which has diverse actions in the brain as a regulator of host defence responses and a mediator of inflammation. Two major agonists, IL-1α and IL-1β bind to a single known functional (type-1) IL-1 receptor (IL-1RI), which associates with an accessory protein (IL-1RAcP) leading to signal transduction. However, recent evidence suggests that some actions of IL-1 in the brain may be independent of IL-1R1 and its classical signalling pathways, pointing to an as yet unidentified functional receptor for IL-1 expressed in the CNS. In this study, cDNA array based gene expression profiling was used to identify possible genes induced by IL-1β independently of IL-1R1. The results show that IL-1β may indeed regulate some genes independently of IL-1R1, suggesting the presence of additional functional IL-1 receptors in the mouse brain. Keywords: experimental treatment (IL-1β), gene ablation (IL-1R1), glia
2006-03-25 | GSE4507 | GEO
Project description:Squalene-based adjuvants are widely utilized in various vaccines because of their effectiveness in enhancing immune responses. Among these, A-910823 and AS03 are recognized squalene-based adjuvants containing α-tocopherol. Although α-tocopherol-containing squalene-based adjuvants are known to enhance humoral immune responses and inflammatory cytokine production, their underlying mechanisms remain unclear. Here, we found that A-910823 regulated IL-1 signaling pathway gene expression and IL-1α and IL-1β protein expressions in an α-tocopherol-dependent manner. While the source of IL-1α was mainly from eosinophils, IL-1β was from wide range of myeloid cells. Mechanistically, IL-1β/CD11c+ cell-IL-1R1/MyD88 axis mediated adjuvant efficacy, however, systemic reactogenicity was induced by the IL-1β/IL-1R1/MyD88/IL-6/cyclooxygenase 2 axis which was unexpectedly distinct mechanism from the local reactogenicity that was mediated by the eosinophil-derived IL-1α/IL-1R1/MyD88 axis. These findings demonstrate that adjuvant efficacy and reactogenicity are regulated by distinct pathways and cell types. This study thus provides novel insights into the mechanisms of adjuvants, providing valuable information to support the future development of effective and safe vaccines.
2026-03-31 | GSE306134 | GEO
Project description:Inflammatory signals can promote tumorigenesis. The pro-inflammatory cytokine interleukin (IL)-1β is overexpressed in many types of tumor; however, it is unclear whether it directly interacted with oncogenes in esophageal squamous cell carcinoma. In this study, we performed RNA sequencing to identify tumorgenesis and recurrence-related factors in ESCC and identified FRAS1-related extracellular matrix protein (FREM)2 as a candidate oncogene. IL-1β and IL-1R1 were upregulated in ESCC tissue, which was accompanied by elevated Frem2 expression. FREM2 formed complex with IL-1R1 at the cell surface and promoted ESCC cell proliferation and migration via activation of nuclear factor-κB–p65/mitogen-activated protein kinase–c-Jun N-terminal kinase signaling. IL-1β stimulation resulted in the upregulation of FREM2 in ESCC cells through inhibition of Forkhead box P1. Increased FREM2 and IL-1R1 levels were correlated with shorter survival time in ESCC patients.
2019-09-03 | GSE119436 | GEO
Project description:We previously established that sensory neurons in the mouse dorsal root ganglia (DRG) express a functional receptor for the proinflammatory cytokine interleukin (IL)-1. We also demonstrated that deletion of the IL-1 receptor type 1 gene, Il1r1, in TRPV1-expressing (+) neurons prevented pain in models of chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis and osteoarthritis. Here, we found a marked sex difference in the abundance of IL-1R1+ neurons, which represented approximately 10% of all DRG neurons in females but only 5% in males. However, male mice exhibited stronger, longer-lasting mechanical hypersensitivity than females after IL-1β injection into the cerebrospinal fluid. In vivo calcium imaging revealed that IL-1β-responsive DRG neurons responded to cutaneous mechanical and capsaicin stimulation. By integrating spatial transcriptomics with single-cell RNA sequencing (scRNA-Seq), we identified a gene signature uniquely marking IL-1R1+ neurons, including genes such as Ada, Cysltr2, Gpr139, Htr1a, Htr1f, Il31ra, Nppb, Npy2r, Nts, P2rx2, Pde4c, and Sst, with Ada and Sst validated at the protein level. Omics analysis revealed that IL-1R1+ DRG neurons form a subset of non-peptidergic type 3 (NP3) sensory neurons, which are linked to inflammatory pain and itch. However, Il1r1 deletion did not affect itch responses to serotonin, histamine, or chloroquine, and these mediators failed to induce calcium activity in IL-1β-responsive DRG neurons. Finally, scRNA-seq identified several genes upregulated in NP3 neurons after IL-1β injection, including Alkal2, Bdnf, and Lcn2, associated with chronic inflammatory pain. Thus, our study unveils novel markers for IL-1R1+ nociceptors and reaffirms their selective role in inflammatory pain.
2026-09-01 | GSE344711 | GEO
Project description:We previously established that sensory neurons in the mouse dorsal root ganglia (DRG) express a functional receptor for the proinflammatory cytokine interleukin (IL)-1. We also demonstrated that deletion of the IL-1 receptor type 1 gene, Il1r1, in TRPV1-expressing (+) neurons prevented pain in models of chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis and osteoarthritis. Here, we found a marked sex difference in the abundance of IL-1R1+ neurons, which represented approximately 10% of all DRG neurons in females but only 5% in males. However, male mice exhibited stronger, longer-lasting mechanical hypersensitivity than females after IL-1β injection into the cerebrospinal fluid. In vivo calcium imaging revealed that IL-1β-responsive DRG neurons responded to cutaneous mechanical and capsaicin stimulation. By integrating spatial transcriptomics with single-cell RNA sequencing (scRNA-Seq), we identified a gene signature uniquely marking IL-1R1+ neurons, including genes such as Ada, Cysltr2, Gpr139, Htr1a, Htr1f, Il31ra, Nppb, Npy2r, Nts, P2rx2, Pde4c, and Sst, with Ada and Sst validated at the protein level. Omics analysis revealed that IL-1R1+ DRG neurons form a subset of non-peptidergic type 3 (NP3) sensory neurons, which are linked to inflammatory pain and itch. However, Il1r1 deletion did not affect itch responses to serotonin, histamine, or chloroquine, and these mediators failed to induce calcium activity in IL-1β-responsive DRG neurons. Finally, scRNA-seq identified several genes upregulated in NP3 neurons after IL-1β injection, including Alkal2, Bdnf, and Lcn2, associated with chronic inflammatory pain. Thus, our study unveils novel markers for IL-1R1+ nociceptors and reaffirms their selective role in inflammatory pain.
2026-09-01 | GSE344702 | GEO
Project description:Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell types. Neuronal IL-1R1 is prominently expressed on the neurons of the dentate gyrus, but its role in mediating behavioral responses to stress is unknown. We hypothesize that IL-1 acts on this subset of hippocampal neurons to influence cognitive and mood alterations with stress. Here, mice subjected to psychosocial stress showed reduced social interaction and impaired working memory, and these deficits were prevented by global IL-1R1 knockout. Selective deletion of IL-1R1 in glutamatergic neurons (nIL-1R1-/-), abundant in the hippocampus wherein the inflammatory-influenced effects were observed, abrogated the stress-induced deficits in social interaction and working memory. RNA-sequencing of microdissected hippocampi revealed that stress increased several canonical pathways (TREM1, NF-κ, complement, IL-6 signaling) and upstream regulators (INFγ, IL-1β, NF-κB, MYD88) associated with inflammation. The inductions of TREM1 signaling, complement, and leukocyte extravasation with stress were reversed by nIL-1R1-/-. Collectively, we show that stress-dependent IL-1R1 signaling in hippocampal neurons represents a novel mechanism by which inflammation is perpetuated and social interactivity and working memory are modulated.
2020-04-24 | GSE149195 | GEO
Project description:The somatic JAK2V617F mutation is found in a majority of patients with myeloproliferative neoplasms (MPN). Chronic inflammation is often associated with MPN, but the role of inflammation in the pathogenesis of MPN remains elusive. Expression of interleukin-1 (IL-1), a key regulator of inflammation, is found elevated in MPN. Here, we show that increased IL-1β enhances myeloid cell expansion and promotes the development of bone marrow (BM) fibrosis in heterozygous Jak2V617F mouse model of MPN. Genetic deletion of IL-1 receptor 1 (IL-1R1) preferentially inhibited the expansion of Jak2 mutant hematopoietic stem/progenitor cells. Furthermore, IL-1R1 deletion or blockade with anti-IL-1R1 antibody significantly reduced leukocytosis and splenomegaly, and markedly inhibited BM fibrosis in homozygous Jak2V617F mutant mice. Collectively, our results suggest that IL-1 signaling plays an important role in progression to BM fibrosis in MPN, and targeting of IL-1R1 could be a useful strategy for the treatment of myelofibrosis.
2022-08-05 | GSE180339 | GEO
Project description:Aged hematopoietic stem cells (HSCs) display myeloid-biased differentiation and reduced regenerative potential. In this study, we uncover that P-selectin (Selp) marks a subset of aged HSCs with reduced repopulation capacity. This population of HSCs expresses a prominent aging transcriptome. Overexpression of Selp in young HSCs impaired long-term reconstitution potential and repressed erythropoiesis. We show that IL-1β is elevated in aged bone marrow and administration of IL-1β induces expression of Selp and other aging-associated genes in HSCs. Finally, we demonstrate that transplantation of aged HSCs into young recipients restores a young-like transcriptome, specifically by repressing pro-inflammatory pathways, highlighting the important role of the bone marrow microenvironment in HSC aging.
2023-01-02 | GSE194273 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:The importance of unanchored Ub in innate immunity has been shown only for a limited number of unanchored Ub-interactors. We investigated what additional cellular factors interact with unanchored Ub and whether unanchored Ub plays a broader role in innate immunity. To identify unanchored Ub-interacting factors from murine lungs, we used His-tagged recombinant poly-Ub chains as bait. These chains were mixed with lung tissue lysates and protein complexes were isolated with Ni-NTA beads. Sample elutions were subjected to mass spectrometry (LC-MSMS) analysis.
2022-02-28 | PXD031365 | Pride