Project description:To reveal early responses to one of septic agents, lipopolysaccharide (LPS), in tissue resident macrophages, we isolated Kupffer cells as well as alveolar macrophages from bolus LPS-injected mice at 1 and 4 hours (hr) of early time points and performed quantitative RNA sequencing
Project description:Uncontrolled microglial activation may lead to development of inflammation-induced brain damage. Here we uncover a ribosome-based mechanism/check point involved in control of the innate immune response and microglial activation. Using an in vivo model-system for analysis of the dynamic translational state of microglial ribosomes with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly up-regulated and ribosome-associated mRNAs were not translated resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA and immunomodulatory/homeostatic protein signature. We find that this is due to specific translational suppression of highly expressed mRNAs through a 3’UTR-mediated mechanism involving the RNA binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia.
Project description:Hypothalamic dysfunction is a key pathological factor in inflammation-associated depression. In the present study, isobaric tags for relative-absolute quantitation (iTRAQ) combined with mass spectrometry were employed to detect the proteomes in the hypothalamus of the lipopolysaccharide (LPS)-induced depression mouse. A total of 187 proteins were differentially expressed compared with the control group. The results indicated altered molecules were clustered into Ephrin receptor signalling; glutamatergic transmission, and inflammation-related signalling. Ephrin type-B receptor 2 (EPHB2), a transmembrane receptor protein in Ephrin receptor signalling, was significantly elevated and interacted with the accumulated NMDAR subunit GluN2A in the hypothalamus. Additionally, molecules involved in synaptic plasticity regulation, such as hypothalamic postsynaptic density protein-95 (PSD-95), p-AKT and brain-derived neurotrophic factor (BDNF), were significantly altered in the LPS-induced depressed group. It might be an underlying pathogenesis that the EPHB2-GluN2A-AKT cascade regulates synaptic plasticity in depression. EPHB2 can be a potential therapeutic target in the correction of glutamatergic transmission dysfunction. In summary, our findings point to the previously undiscovered molecular underpinnings of the pathophysiology in the hypothalamus of inflammation-associated depression and offer potential targets to develop antidepressants.
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with Lipopolysaccharide (LPS) labeled with Cy5- time course with repeats Keywords: ordered
Project description:Using RNAseq, we compared the mRNA profiles of microglia in wild type or microglia-specific A20 knockout mice. These mice were either untreated or intraperitoneally injected with LPS (3.5 mg/kg).
Project description:Lipopolysaccharide is a Microbe Associated Molecular Pattern (MAMP) that is known to induce defense responses in plants. We have shown that treatment of rice leaves with Xoo LPS induces callose deposition, reactive oxygen production and enhances resistance against subsequent infection by the pathogen. We have performed transcriptional profiling of rice leaves that are treated with Xoo LPS to identify differentially expressed genes. Xoo LPS was injected into mid-veins of rice leaves and RNA was isolated 15 hours later.
Project description:Using RNAseq, we compared the mRNA profiles of CD45hi cells in the brain of wild type or myeloid-specific A20 knockout mice. These mice were either untreated or intraperitoneally injected with LPS (3.5 mg/kg).
Project description:Comparison of mouse macrophage responses to 12-o-tetradecanoylphorbol-13-acetate (TPA), lipopolysaccharide (LPS), and LPS plus dexamethasone between wild-type and NCoR-/- mice.
Project description:IL-6 has been described to be a critical cytokine in mediating the febrile response because neither IL-6 knockout mice injected with peripheral lipopolysaccharide (LPS) or IL-1β, nor animals treated with IL-6 antiserum develop fever. However, the fever response is developed in IL-6 KO mice following intracerebroventricular administration of Prostaglandin E2 which is the principal mediator of the febrile response.
Project description:Brain aggregates of α-synuclein (α-syn) characterizes a group of diseases defined as synucleinopathies. Recent studies implicate neuroinflammation as one of the central pathogenic mechanisms. However, how inflammation is linked to the α-syn pathology is still unknown. We wanted to address this by a ‘double-hit’ approach. Three weeks after intra-striatal injections of human α-syn pre-formed fibrils (PFF), mice were subjected for 3 weeks to repeated intraperitoneal injections of low concentrations (1 mg/ml) of lipopolysaccharide (LPS), a component of gram-negative bacteria. Histological analysis confirmed brain propagation of α-syn aggregation in PFF-injected mice independent of LPS-injections. No motor dysfunction was observed at this stage as measured in the pole test. Spleen immune cell profiling and multiplex cytokine analysis confirmed LPS-induced changes in T- and B-cells populations, monocytes, and neutrophils, and increased brain TNF-α, IL-β, IL-10 and KC/GRO levels. LC-MS/MS analysis in the forebrain area and subsequent downstream ReactomeGSA pathway analysis revealed that PFF-injections induced alterations in mitochondrial metabolism and neurotransmitter signaling. Systemic inflammation resulted in an overrepresentation of complement and coagulation pathways and upregulation of integrin and B cell receptor signaling in the PFF-injected mice.