PXD033002 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TLR4 activation primes human macrophages for non-canonical caspase-4 inflammasome-induced extracellular vesicle secretion |
Description | Human macrophages secrete extracellular vesicles loaded with numerous immunoregulatory proteins. Here we employed high throughput quantitative proteomics to characterize the modulation of vesicle-mediated protein secretion during non-canonical caspase-4/5-dependent inflammasome activation. We show that human macrophages activate robust caspase-4- dependent extracellular vesicle secretion upon transfection of LPS, and this process is also partially dependent on NLRP-3 and caspase-5. Similar effect occurs with delivery of the LPS with E. coli-derived outer membrane vesicles. Moreover, sensitization of the macrophages through TLR4 prior to LPS transfection dramatically augments the EV-mediated protein secretion. Our data demonstrate that this process differs significantly from ATP-induced vesiculation, and is dependent on autocrine interferon signal associated with TLR4 activation. TLR4 activation preceding the non-canonical inflammasome activation significantly enhances vesicle-mediated secretion of inflammasome components caspase-1, ASC and lytic cell death effectors GSDMD, MLKL and NINJ1, suggesting that inflammatory EV transfer may exert paracrine effects in recipient cells. Moreover, using bioinformatic methods, we identify 15-deoxy-delta-12,14-prostaglandin J2 and parthenolide as inhibitors of caspase-4-mediated inflammation and vesicle secretion, indicating potential new therapeutic potential of these anti-inflammatory drugs. |
HostingRepository | PRIDE |
AnnounceDate | 2022-12-01 |
AnnouncementXML | Submission_2022-12-01_07:21:09.408.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | TuulaNyman |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-04-06 07:48:00 | ID requested | |
⏵ 1 | 2022-12-01 07:21:09 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: caspase-4,macrophages, proteomics, extracellular vesicles, interferon, non-canonical inflammasome |
Contact List
TuulaNyman |
contact affiliation | Head of Proteomics |
contact email | tuula.nyman@medisin.uio.no |
lab head | |
TuulaNyman |
contact affiliation | University of Oslo |
contact email | tuula.nyman@medisin.uio.no |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD033002
- Label: PRIDE project
- Name: TLR4 activation primes human macrophages for non-canonical caspase-4 inflammasome-induced extracellular vesicle secretion