PXD033002

PXD033002 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-06 07:48:00	ID requested
⏵ 1	2022-12-01 07:21:09	announced

Dataset with its publication pending

submitter keyword: caspase-4,macrophages, proteomics, extracellular vesicles, interferon, non-canonical inflammasome

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

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PRIDE project URI

• PRIDE
  1. PXD033002
     1. Label: PRIDE project
     2. Name: TLR4 activation primes human macrophages for non-canonical caspase-4 inflammasome-induced extracellular vesicle secretion