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Synergy between 15-...
Synergy between 15-lipoxygenase and secreted PLA2 promotes inflammation by formation of TLR4 agonists from extracellular vesicles
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- Ha, V. T. (author)
- National Institute of Chemistry, Ljubljana, Slovenia
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- Lainscek, D. (author)
- National Institute of Chemistry, Ljubljana, Slovenia
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- Gesslbauer, B. (author)
- University of Graz, Graz, Austria
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- Jarc, E. (author)
- Jozef Stefan Institute, Ljubljana, Slovenia
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- Hyötyläinen, Tuulia, 1971- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik
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- Ilc, N. (author)
- University of Ljubljana, Ljubljana, Slovenia
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- Lakota, K. (author)
- University Medical Centre Ljubljana, Ljubljana, Slovenia
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- Tomsic, M. (author)
- University Medical Centre Ljubljana, Ljubljana, Slovenia
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- van de Loo, F. A. (author)
- Radboud University Medical Center, Nijmegen, Netherlands
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- Bochkov, V. (author)
- University of Graz, Graz, Austria
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- Petan, T. (author)
- Jozef Stefan Institute, Ljubljana, Slovenia
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- Jerala, R. (author)
- National Institute of Chemistry, Ljubljana, Slovenia
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- Keber, M. Mancek (author)
- National Institute of Chemistry, Ljubljana, Slovenia
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(creator_code:org_t)
- John Wiley & Sons, 2021
- 2021
- English.
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In: FEBS Open Bio. - : John Wiley & Sons. - 2211-5463. ; 11:Suppl. 1, s. 480-480
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- 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).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- vet (subject category)
- art (subject category)
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- By the author/editor
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Ha, V. T.
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Lainscek, D.
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Gesslbauer, B.
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Jarc, E.
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Hyötyläinen, Tuu ...
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Ilc, N.
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show more...
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Lakota, K.
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Tomsic, M.
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van de Loo, F. A ...
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Bochkov, V.
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Petan, T.
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Jerala, R.
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Keber, M. Mancek
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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FEBS Open Bio
- By the university
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Örebro University