PXD003971

PXD003971 is an original dataset announced via ProteomeXchange.

Title	Eicosadomics, proteomics and metabolomics of inflammatory stimulated human fibroblasts reveals specific functions related to chronic inflammation - secreted proteins of dexamethasone-treated inflammatory stimulated cells
Description	Fibroblasts have only recently been identified as important effector cells in inflammation. In this study, human dermal fibroblasts were inflammatory stimulated with interleukin-1beta and comprehensively analysed with respect to proteins, eicosanoids and metabolites. For eicosadomics, we have established a data-dependent shotgun analysis method capable of identifying inflammation-regulated lipids of yet unknown function. Several classical inflammatory agonists were found induced, including PGA2, PGB2, PGE2 and TXB2, but also modulators such as PGA3 and PGE3, while 8-HETE and several HODE family members remained unaffected. Using targeted metabolomics, several acylcarnithins, phosphatitylcholins and sphingomyelins were found significantly downregulated. Proteome profiling with orbitrap-MS demonstrated the strong induction of several chemokines, metalloproteinases and other effector molecules. Treatment of stimulated fibroblasts with dexamethasone almost completely abrogated the formation of all inflammation-induced eicosanoids and restored levels of acylcarnithins back to normal. As expected, the secretion of IL-6, MMP1, MMP3, CXCL2 and CXCL3 was strongly down-regulated. However, instead of counter-regulating, dexamethasone further enhanced consequences of inflammatory stimulation with respect to CXCL1, CXCL6, complement C3 as well as sphingomyelins. Shotgun secretome data were confirmed by targeted analysis with triple-quadrupol-MS. These molecules have been described to be involved in chronic inflammation. In peripheral blood mononuclear cells, actually dexamethasone successfully downregulated the formation of all detectable inflammation mediators. The present data suggest that successful pharmacological abrogation of the formation of lipid inflammatory mediators in fibroblasts may not suffice to suppress the release of several other powerful inflammatory mediators which we thus understand to be capable of establishing chronic inflammation states.
HostingRepository	PRIDE
AnnounceDate	2017-02-22
AnnouncementXML	Submission_2017-02-22_05:55:57.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD003971
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Christopher Gerner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-04-14 04:42:38	ID requested
⏵ 1	2017-02-22 05:55:58	announced

Tahir A, Bileck A, Muqaku B, Niederstaetter L, Kreutz D, Mayer RL, Wolrab D, Meier SM, Slany A, Gerner C, Combined Proteome and Eicosanoid Profiling Approach for Revealing Implications of Human Fibroblasts in Chronic Inflammation. Anal Chem, 89(3):1945-1954(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Human fibroblasts, chronic inflammation, shotgun proteomics, shotgun lipidomics, eicosadomics, metabolomics, multiple reaction monitoring

Christopher Gerner
contact affiliation	University of Vienna, Faculty of Chemistry, Department of Analytical Chemistry
contact email	christopher.gerner@univie.ac.at
lab head
Christopher Gerner
contact affiliation	University of Vienna
contact email	christopher.gerner@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003971
     1. Label: PRIDE project
     2. Name: Eicosadomics, proteomics and metabolomics of inflammatory stimulated human fibroblasts reveals specific functions related to chronic inflammation - secreted proteins of dexamethasone-treated inflammatory stimulated cells