PXD040933

PXD040933 is an original dataset announced via ProteomeXchange.

Title	Effects of lysine deacetylase inhibitor treatment on LPS responses of alveolar-like macrophages
Description	Macrophages are key immune cells in tissues that are able to adapt their metabolic phenotype in response to different stimuli. Lysine deacetylases are important enzymes for regulating inflammatory gene expression and their inhibitors have anti-inflammatory effects in models of chronic obstructive pulmonary disease (COPD). We hypothesized that these anti-inflammatory effects may be driven by or associated with metabolic changes in macrophages. To validate this hypothesis, we used an unbiased and a targeted proteomic approach to investigate metabolic enzymes and LC- and GC-MS to quantify metabolites in combination with functional parameters in primary murine alveolar-like macrophages after lipopolysaccharide (LPS)-induced activation with and without lysine deacetylase inhibitors. We found that lysine deacetylase inhibitor treatment resulted in reduced production of inflammatory mediators such as TNF-α and IL-1β. However, only minor changes in macrophage metabolism were observed, as only one of the deacetylase inhibitors slightly increased mitochondrial respiration. However, lysine deacetylase inhibition specifically enhanced expression of proteins involved in ubiquitination, and this may be a potential driver of the anti-inflammatory effects of lysine deacetylase inhibitors. Our data illustrate that a multi-omics approach is necessary to gain a better understanding of how macrophages interact with cues from their environment. More detailed insight into the molecular mechanisms of KDAC inhibition is needed and investigating ubiquitination seems a promising next step. This is important as conventional anti-inflammatory drugs like corticosteroids have low effectiveness in many patients and novel therapeutic strategies are urgently needed.
HostingRepository	PRIDE
AnnounceDate	2024-02-21
AnnouncementXML	Submission_2024-02-21_05:34:45.119.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justina Clarinda Wolters
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-17 05:35:09	ID requested
⏵ 1	2024-02-21 05:34:46	announced

10.1093/jleuko/qiad121;

Russo S, Kwiatkowski M, Wolters JC, Gerding A, Hermans J, Govorukhina N, Bischoff R, Melgert BN, Effects of lysine deacetylase inhibitor treatment on LPS responses of alveolar-like macrophages. J Leukoc Biol, 115(3):435-449(2024) [pubmed]

submitter keyword: DIA proteomics, alveolar-like macrophages, LPS activation, KDAC inhibition, mouse

Justina Clarinda
contact affiliation	Department of Pediatrics, UMCG
contact email	j.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliation	UMCG
contact email	j.c.wolters@umcg.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD040933

PRIDE project URI

• PRIDE
  1. PXD040933
     1. Label: PRIDE project
     2. Name: Effects of lysine deacetylase inhibitor treatment on LPS responses of alveolar-like macrophages