SwePub - sökning: WFRF:(Lakota K)

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1.	Ambrozic, A, et al. (författare) Corrigendum 2017 Ingår i: Journal of thrombosis and haemostasis : JTH. - : Elsevier BV. - 1538-7836. ; 15:6, s. 1236-1236 Tidskriftsartikel (refereegranskat)
2.	Ha, V. T., et al. (författare) Synergy between 15-lipoxygenase and secreted PLA2 promotes inflammation by formation of TLR4 agonists from extracellular vesicles 2021 Ingår i: FEBS Open Bio. - : John Wiley & Sons. - 2211-5463. ; 11:Suppl. 1, s. 480-480 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Damage assoiated molecular patterns (DAMPs) are endogenous ligands that induce innate immune response, thus promoting sterile inﬂammation. During oxidative stress, stress-derived EVs (stressEVs) were found to activate Toll-like receptor 4 (TLR4), but the activating ligands were not fully determined. Additionally, several enzymes such as 15-lipoxygenase (15-LO) and secreted phospholipase A2 (sPLA2) are induced during inﬂammation and were suggested to promote DAMP formation. Stress-EVs were produced from HEK293 exposed to 10uM A23187 and isolated with ultracentrifugation. 20:4 lysoPI was oxidized for 10 min with 15-LO. SynEVs were prepared from phospholipids (PLs), oxidized with 15-LO and hydrolyzed with sPLA2. Activity was measured by qPCR and ELISA on wt and KO cells. Ox 20:4 lysoPI was analyzed by MS. sPLA2 activity was measured in synovial ﬂuid from patients using ﬂuorometric assay. K/BxN serum transfer induced arthritis model on wt and TLR4 KO mice(C57Bl/6 mice) with sPLA2-IIA injection was performed. StressEVs released after oxidative stress were found to activate TLR4with a gene proﬁle different from agonist lipopolysaccharide. StressEVs, 15-LO oxidized synEVs, but only 15-LO oxidized lysoPLs activated cytokine expression through TLR4/MD-2.Hydroxy, hydroperoxy and keto products of 20:4 lysoPI oxidation were determined by MS and they activated the same gene pattern as stressEVs. Furthermore, sPLA2 activity, which we detected in the SF from patients, promoted formation of TLR4 agonists after 15-LO oxidation. Injection of sPLA2-IIA into mice promoted K/BxN serum induced arthritis in TLR4-dependent manner. Both 15-LO and sPLA2 are induced during inﬂammation, therefore these results imply the role of oxidized lysoPLs in stressEVs in promoting sterile inﬂammation through TLR4 signaling. The formation of TLR4 agonists is enzyme driven so it provides an opportunity for therapy without compromising innate immunity against pathogens (Ha VT. et al., PNAS 2020).

Ha, V. T., et al. (författare)
Synergy between 15-lipoxygenase and secreted PLA2 promotes inflammation by formation of TLR4 agonists from extracellular vesicles
2021
Ingår i: FEBS Open Bio. - : John Wiley & Sons. - 2211-5463. ; 11:Suppl. 1, s. 480-480
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Damage assoiated molecular patterns (DAMPs) are endogenous ligands that induce innate immune response, thus promoting sterile inﬂammation. During oxidative stress, stress-derived EVs (stressEVs) were found to activate Toll-like receptor 4 (TLR4), but the activating ligands were not fully determined. Additionally, several enzymes such as 15-lipoxygenase (15-LO) and secreted phospholipase A2 (sPLA2) are induced during inﬂammation and were suggested to promote DAMP formation. Stress-EVs were produced from HEK293 exposed to 10uM A23187 and isolated with ultracentrifugation. 20:4 lysoPI was oxidized for 10 min with 15-LO. SynEVs were prepared from phospholipids (PLs), oxidized with 15-LO and hydrolyzed with sPLA2. Activity was measured by qPCR and ELISA on wt and KO cells. Ox 20:4 lysoPI was analyzed by MS. sPLA2 activity was measured in synovial ﬂuid from patients using ﬂuorometric assay. K/BxN serum transfer induced arthritis model on wt and TLR4 KO mice(C57Bl/6 mice) with sPLA2-IIA injection was performed. StressEVs released after oxidative stress were found to activate TLR4with a gene proﬁle different from agonist lipopolysaccharide. StressEVs, 15-LO oxidized synEVs, but only 15-LO oxidized lysoPLs activated cytokine expression through TLR4/MD-2.Hydroxy, hydroperoxy and keto products of 20:4 lysoPI oxidation were determined by MS and they activated the same gene pattern as stressEVs. Furthermore, sPLA2 activity, which we detected in the SF from patients, promoted formation of TLR4 agonists after 15-LO oxidation. Injection of sPLA2-IIA into mice promoted K/BxN serum induced arthritis in TLR4-dependent manner. Both 15-LO and sPLA2 are induced during inﬂammation, therefore these results imply the role of oxidized lysoPLs in stressEVs in promoting sterile inﬂammation through TLR4 signaling. The formation of TLR4 agonists is enzyme driven so it provides an opportunity for therapy without compromising innate immunity against pathogens (Ha VT. et al., PNAS 2020).

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