PXD074418-1

PXD074418 is an original dataset announced via ProteomeXchange.

Title	Exploring the proteomic landscape of THP-1 monocytes through two-challenge LPS induction
Description	Proteome remodelling is central to the regulation of innate immune activation, yet the temporal organisation of protein networks engaged during primary and repeated lipopolysaccharide stimulation remains poorly defined. In the present study, label-free quantitative mass spectrometry-based proteomics was combined with targeted interaction profiling of the regulatory pseudo-kinase IRAK3 to map dynamic protein changes in human monocytes across early (30 min) and later (2 h)activation states after repeated stimulation in a tolerance model induced by LPS. Early responses featured coordinated induction of signalling proteins, rapid reorganisation of chromatin-associated factors, RNA-binding proteins, and components of the translational apparatus. By two hours, the proteome shifted toward metabolic enzymes, antigen-processing machinery, vesicle-associated proteins, and chaperone systems; reflecting a regulatory programme that supports sustained activation while maintaining protein homeostasis. Repeated stimulation produced a tolerant phenotype driven by quantitative redistribution of inflammatory, metabolic, and proteostatic proteins rather than by major changes in protein identity and was associated with strong induction of IRAK3 and stress-responsive regulators. Targeted co-immunoprecipitation identified both known and previously uncharacterised IRAK3-associated protein candidates linked to RNA regulation, kinase signalling, ubiquitin-mediated pathways, redox control, and damage-associated molecular pattern responses. Together, these findings define a detailed temporal framework of protein-level adaptations governing monocyte activation and tolerance and expand current understanding of IRAK3-centred regulatory networks integrating signalling, metabolic, and proteostatic processes in innate immunity.
HostingRepository	PRIDE
AnnounceDate	2026-08-21
AnnouncementXML	Submission_2026-08-20_20:39:53.401.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cassandra Cianciarulo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-12 21:41:33	ID requested
⏵ 1	2026-08-20 20:39:54	announced

10.1016/J.BBAPAP.2026.141171;

submitter keyword: Innate immunity

lipopolysaccharides (LPS)

monocytes

proteomics

sepsis

Interleukin-1 receptor associated kinase 3 (IRAK3).

Helen Ruth Irving
contact affiliation	Irving Laboratory, Department of Rural Clinical Science, La Trobe University, Australia
contact email	h.irving@latrobe.edu.au
lab head
Cassandra Cianciarulo
contact affiliation	La Trobe University
contact email	c.cianciarulo@latrobe.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074418
     1. Label: PRIDE project
     2. Name: Exploring the proteomic landscape of THP-1 monocytes through two-challenge LPS induction