PXD019824

PXD019824 is an original dataset announced via ProteomeXchange.

Title	Oxysterols Modify NLRP2 in Epithelial Cells, Identifying a Mediator of Ozone-induced Inflammation.
Description	Ozone (O3) is a prevalent air pollutant that causes lung inflammation following exposure. Previous studies demonstrate that O3 oxidizes lipids, such as cholesterol, in the airway to produce oxidized cholesterol products (oxysterols), such as secosterol-A (secoA), which form covalent linkages preferentially with lysine residues and consequently modify protein function. The breadth of proteins modified by this oxysterol as well as the biological consequences in the lung are unknown. Using an alkynyl-tagged form of secosterol-A and shotgun proteomics, we identified NLR Family Pyrin Domain Containing 2 (NLRP2) to be adducted at lysine (K1019) in the terminal leucine-rich-repeat, a known regulatory region for NLR proteins. We characterized NLRP2 expression in airway epithelial cells and used CRISPR-Cas9 knockout and shRNA knockdown of NLRP2 for analysis of inflammasome complex activity and pro-inflammatory mediator production following O3 exposure. We observed an increase in caspase-1 activity in response to O3, which was not altered by knocked down NLRP2 expression. O3-induced pro-inflammatory gene expression for CXCL1, CXCL2, and IL8 was further enhanced in NLRP2 knockout cells. Together, our findings uncover NLRP2 as a highly abundant, key component of pro-inflammatory signaling pathways in airway epithelial cells and formation of oxysterol-NLRP2 adduct as a novel mediator of O3-induced inflammation.
HostingRepository	PRIDE
AnnounceDate	2021-06-21
AnnouncementXML	Submission_2021-06-20_22:30:46.393.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD019824
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Hye-Young Kim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-16 23:22:56	ID requested
⏵ 1	2021-06-20 22:30:47	announced

Perryman A, Speen AM, Kim HH, Hoffman JR, Clapp PW, Rivera Martin W, Snouwaert JN, Koller BH, Porter NA, Jaspers I, Oxysterols Modify NLRP2 in Epithelial Cells, Identifying a Mediator of Ozone-induced Inflammation. Am J Respir Cell Mol Biol, 65(5):500-512(2021) [pubmed]

submitter keyword: Human, LC-MSMS, airway epithelium, lung inflammasome,alkynylated secosterol, click, protein modification, ozone, secosterols

Ned A. Porer, Hye-Young H. Kim
contact affiliation	Department of Chemistry, Vanderbilt University
contact email	hye-young.h.kim@vanderbilt.edu
lab head
Hye-Young Kim
contact affiliation	Vanderbilt University
contact email	hye-young.h.kim@vanderbilt.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019824
     1. Label: PRIDE project
     2. Name: Oxysterols Modify NLRP2 in Epithelial Cells, Identifying a Mediator of Ozone-induced Inflammation.