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Yo Otsu

Publications and source records attributed to Yo Otsu.

7 recordsLinked to original sources
PubMed2026

IL-33 Drives Inflammatory Changes and Extracellular Trap Formation in Eosinophils Involving Oxidised LDL and Complement Pathways.

BACKGROUND: IL-33 levels are elevated in the airways of patients with eosinophilic diseases, and IL-33 receptor expression on eosinophils is upregulated in type 2-high environments. However, the role of IL-33 in the regulation of human eosinophils remains unclear. OBJECTIVE: To elucidate the inflammatory effects of IL-33 on the cellular function of human eosinophils. METHODS: Blood eosinophils were stimulated with IL-33, TNF-α, oxidised low-density lipoprotein (oxLDL) and complement fragments (C3a and C5a). Multi-omics analyses, including transcriptomics and proteomics, were performed. Extracellular trap formation (ETosis) was assessed by SYTOX nucleic acid staining and was visualised by immunofluorescence and transmission electron microscopy. RESULTS: Multi-omics analyses revealed an IL-33- and TNF-α-induced inflammatory gene signature characterised by the upregulation of cell surface markers (oxLDL receptor 1, CD22, CD4 and ICAM-1) and inflammatory mediators (C3, CCL3/4 and IL1A/B). CD22 upregulation was specific to IL-33 stimulation. Eosinophils derived from nasal polyps exhibited a gene expression profile similar to that of IL-33-stimulated eosinophils. Functional assays demonstrated that oxLDL and complement fragments differentially prolonged eosinophil survival and altered the expression of adhesion molecules. OxLDL- and complement fragment-induced gene signatures were partly detected in eosinophils derived from nasal polyps. Furthermore, IL-33 triggered ETosis via NADPH oxidase, mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. CONCLUSIONS: IL-33, in conjunction with oxLDL and the complement cascade, induces inflammatory changes in eosinophils, promoting an ETosis-prone phenotype. These pathways represent potential therapeutic targets in refractory eosinophilic diseases.

Humans↗
PubMed2004

Optical postsynaptic measurement of vesicle release rates for hippocampal synapses undergoing asynchronous release during train stimulation.

Developing hippocampal neurons in microisland culture were found to undergo rapid depression of excitatory synaptic activity caused by consumption of their readily releasable pool (RRP) of vesicles in response to 20 Hz trains of stimulation. Associated with depression was a switch to an asynchronous release mode that maintained transmission at a high steady-state rate equivalent to approximately 2.1 RRPs per second. We have applied postsynaptic Ca2+ imaging to directly monitor these asynchronous release events to estimate both the steady rate of transmitter release and the number of quanta within the RRP at individual hippocampal synapses. Based on the frequency of asynchronous release measured at individual synapses postsynaptically using Ca2+ imaging (5-17 sec after train stimulation) and with knowledge of the time course by which asynchronous release rates decay, we estimate that individual hippocampal synapses exhibit (in response to train stimulation) peak release rates of up to 21 quanta per second from an RRP that contains, on average, 10 quanta. Use-dependent block of evoked synaptic activity by MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate] confirmed that synapses undergoing asynchronous release are not significantly different from the general population with regard to their composition of NMDA receptor and/or release probability. Given that high-frequency trains deplete the synapse of readily releasable quanta (and that these release rates can only be maintained for a few seconds), these high rates of asynchronous release likely reflect refilling of vesicles from a reserve pool and not necessarily the continuous action of a relatively slow clathrin- and endosome-dependent process.

Animals↗
PubMed2004

Competition between phasic and asynchronous release for recovered synaptic vesicles at developing hippocampal autaptic synapses.

Developing hippocampal neurons in microisland culture undergo rapid and extensive transmitter release-dependent depression of evoked (phasic) excitatory synaptic activity in response to 1 sec trains of 20 Hz stimulation. Although evoked phasic release was attenuated by repeated stimuli, asynchronous (miniature like) release continued at a high rate equivalent to approximately 2.8 readily releasable pools (RRPs) of quanta/sec. Asynchronous release reflected the recovery and immediate release of quanta because it was resistant to sucrose-induced depletion of the RRP. Asynchronous and phasic release appeared to compete for a common limited supply of release-ready quanta because agents that block asynchronous release, such as EGTA-AM, led to enhanced steady-state phasic release, whereas prolongation of the asynchronous release time course by LiCl delayed recovery of phasic release from depression. Modeling suggested that the resistance of asynchronous release to depression was associated with its ability to out-compete phasic release for recovered quanta attributable to its relatively low release rate (up to 0.04/msec per vesicle) stimulated by bulk intracellular Ca2+ concentration ([Ca2+]i) that could function over prolonged intervals between successive stimuli. Although phasic release was associated with a considerably higher peak rate of release (0.4/msec per vesicle), the [Ca2+]i microdomains that trigger it are brief (1 msec), and with asynchronous release present, relatively few quanta can accumulate within the RRP to be available for phasic release. We conclude that despite depression of phasic release during train stimulation, transmission can be maintained at a near-maximal rate by switching to an asynchronous mode that takes advantage of a bulk presynaptic [Ca2+]i.

Animals↗
PubMed2003

Developmental decrease in NMDA receptor desensitization associated with shift to synapse and interaction with postsynaptic density-95.

NMDA receptors (NMDARs) play a crucial role in neuronal development, synaptic plasticity, and excitotoxicity; therefore, regulation of NMDAR function is important in both physiological and pathological conditions. Previous studies indicate that the NMDAR-mediated synaptic current decay rate increases during development because of a switch in receptor subunit composition, contributing to developmental changes in plasticity. To test whether NMDAR desensitization also changes during development, we recorded whole-cell NMDA-evoked currents in cultured rat hippocampal neurons. We found that glycine-independent desensitization of NMDARs decreases during development. This decrease was not dependent on a switch in subunit composition or differential receptor sensitivity to agonist-, Ca2+-, or Zn2+-induced increase in desensitization. Instead, several lines of evidence indicated that the developmental decrease in desensitization was tightly correlated with synaptic localization of the receptor, suggesting that association of NMDARs with proteins selectively expressed at synapses in mature neurons might account for developmental alterations in desensitization. Accordingly, we tested the role of interactions between PSD-95 (postsynaptic density-95) and NMDARs in regulating receptor desensitization. Overexpression of PSD-95 reduced NMDAR desensitization in immature neurons, whereas agents that interfere with synaptic targeting of PSD-95, or induce movement of NMDARs away from synapses and uncouple the receptor from PSD-95, increased NMDAR desensitization in mature neurons. We conclude that synaptic localization and association with PSD-95 increases stability of hippocampal neuronal NMDAR responses to sustained agonist exposure. Our results elucidate an additional mechanism for differentially regulating NMDAR function in neurons of different developmental stages or the response of subpopulations of NMDARs in a single neuron.

Animals↗
PubMed2003

Miniature transmitter release: accident of nature or careful design?

Miniature transmitter release results from the constitutive low-level release of individual vesicles of neurotransmitter. Since the 1950s, this form of synaptic transmission has largely been thought to reflect a leaky evoked-release mechanism, and it was not clear whether it had a function of its own. Recent data challenge this view and suggest that miniature release can affect both the local chemistry of synapses and the network properties of neurons.

Animals↗
PubMed2002

Differential regulation of synaptic and extra-synaptic NMDA receptors.

A variety of processes limit NMDA (N-methyl-D-aspartate) receptor (NMDAR) activity in response to agonist exposure, including rundown--the decline of peak current with repeated, sustained agonist application. Here we report that calcium and tyrosine phosphorylation differentially regulate rundown of synaptic versus extrasynaptic NMDAR-mediated current in rat hippocampal pyramidal neurons.

Animals↗