PXD035125-1

PXD035125 is an original dataset announced via ProteomeXchange.

Title	¬The EGFR/ErbB inhibitor neratinib promotes apoptosis and clearance by airway macrophages
Description	Dysregulated neutrophilic inflammation can be highly destructive in chronic inflammatory diseases due to prolonged neutrophil lifespan and continual release of histotoxic mediators in inflamed tissues. Inducing neutrophil apoptosis, an immunologically silent form of cell death, may be beneficial in these diseases, provided that the apoptotic neutrophils are efficiently cleared from the tissue. Our previous research identified ErbB inhibitors as able to induce neutrophil apoptosis and reduce neutrophilic inflammation both in vitro and in vivo (Rahman et al. 2019). Here we expand on that work using a clinical ErbB inhibitor, neratinib, which has the potential to be repurposed in inflammatory diseases. We show that neratinib reduces neutrophilic migration to an inflammatory site in zebrafish larvae. Neratinib upregulates efferocytosis and reduces the number of dead neutrophils in mouse models of acute, but not chronic, lung injury, suggesting the drug may have therapeutic benefits in acute inflammatory settings. Phosphoproteomics analysis of human neutrophils shows that neratinib modifies the phosphorylation of proteins regulating apoptosis, migration and efferocytosis. This work identifies a potential efficacious mechanism for neratinib in acute lung inflammation by upregulating the clearance of dead neutrophils, and examination of the neutrophil phosphoproteome gives insight into the mechanisms by which this may be occurring.
HostingRepository	PRIDE
AnnounceDate	2022-07-22
AnnouncementXML	Submission_2022-07-22_01:44:49.249.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-06 14:36:05	ID requested
⏵ 1	2022-07-22 01:44:49	announced

Dataset with its publication pending

submitter keyword: neratinib, macrophage, neutrophil

Mark Collins
contact affiliation	School of Biosciences University of Sheffield Firth Court, Western Bank University of Sheffield Sheffield, S10 2TN United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035125
     1. Label: PRIDE project
     2. Name: ¬The EGFR/ErbB inhibitor neratinib promotes apoptosis and clearance by airway macrophages