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PXD052433-1

PXD052433 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLPS-induced TIR domain complex acetylation activated TLR4/MAL/MyD88 signal pathway in sepsis
DescriptionAmong the diseases caused by Toll-like receptor 4 (TLR4) abnormal activation by bacterial endotoxin, sepsis is the most dangerous one. The reprogramming of macrophages plays a crucial role in orchestrating the pathogenesis of sepsis. However, the precise mechanism underlying TLR4 activation in macrophages remained incompletely understood. Our studies revealed that upon lipopolysaccharide (LPS) stimulation, CREB-binding protein (CBP) was recruited to the TLR4 signalosome complex and resulted in pronounced acetylation in the TIR domains of TLR4, Myeloid differentiation factor 88 (MyD88) and MyD88 adapter-like (MAL), which significantly enhanced the activation of the NF-κB signaling pathway and polarization of M1 macrophages. In sepsis patients, significantly elevated TLR4-TIR acetylation was detected in CD16+ monocytes combined with elevated expression of M1 macrophage markers and production of pro-inflammatory cytokines. In contrast, histone deacetylase 1 (HDAC1) served as a key deacetylase in the deacetylation of the TIR domain complex. The inhibition of HDAC1 accelerated sepsis-associated syndromes, while the inhibition of CBP alleviated this process. Overall, our findings highlighted the crucial role of TIR domain complex acetylation in the regulation of inflammatory immune response and suggested that the reversible acetylation of the complex emerged as a promising therapeutic target for M1 macrophages during the progression of sepsis.
HostingRepositoryPRIDE
AnnounceDate2024-08-01
AnnouncementXMLSubmission_2024-08-01_05:18:01.267.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterXingxing Wu
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-05-21 02:09:37ID requested
12024-08-01 05:18:01announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: TLR4,Myd88,sepsis
Contact List
Clinical Medicine
contact affiliationZhejiang Provincial People’s Hospital
contact email18504292075@163.com
lab head
Xingxing Wu
contact affiliation15869047982
contact email2950889085@qq.com
dataset submitter
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Dataset FTP location
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