Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018099 (
gout
)
5,192
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Damage-associated endogenous molecules induce innate immune response, thus making sterile inflammation medically relevant. Stress-derived extracellular vesicles (stressEVs) released during oxidative stress conditions were previously found to activate Toll-like receptor 4 (TLR4), resulting in expression of a different pattern of immune response proteins in comparison to lipopolysaccharide (LPS), underlying the differences between pathogen-induced and sterile inflammation. Here we report that synergistic activities of
15-lipoxygenase
(15-LO) and secreted phospholipase A
2
(sPLA
2
) are needed for the formation of TLR4 agonists, which were identified as lysophospholipids (lysoPLs) with oxidized unsaturated acyl chain. Hydroxy, hydroperoxy, and keto products of 2-arachidonoyl-lysoPI oxidation by 15-LO were identified by mass spectrometry (MS), and they activated the same gene pattern as stressEVs. Extracellular PLA
2
activity was detected in the synovial fluid from rheumatoid arthritis and
gout
patients. Furthermore, injection of sPLA
2
promoted K/BxN serum-induced arthritis in mice, whereby ankle swelling was partially TLR4 dependent. Results confirm the role of oxidized lysoPL of stressEVs in sterile inflammation that promotes chronic diseases. Both 15-LO and sPLA
2
enzymes are induced during inflammation, which opens the opportunity for therapy without compromising innate immunity against pathogens.
...
PMID:Synergy between 15-lipoxygenase and secreted PLA
2
promotes inflammation by formation of TLR4 agonists from extracellular vesicles. 3297 91
