Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury
Aim: Endotoxin-mediated liver inflammation is a key component of many acute and chronic liver diseases contributing to liver damage, fibrosis and eventually organ failure. Here, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate rega...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 24, 2018
|
| In: |
PLOS ONE
Year: 2018, Volume: 13, Issue: 5 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0197836 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pone.0197836 Verlag, kostenfrei, Volltext: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197836 
|
| Author Notes: | Johannes Maximilian Ludwig, Yuling Zhang, Walee Chamulitrat, Wolfgang Stremmel, Anita Pathil |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1578163021 | ||
| 003 | DE-627 | ||
| 005 | 20230426230819.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180801s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0197836 |2 doi | |
| 035 | |a (DE-627)1578163021 | ||
| 035 | |a (DE-576)508163021 | ||
| 035 | |a (DE-599)BSZ508163021 | ||
| 035 | |a (OCoLC)1264004349 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Ludwig, Johannes Maximilian |d 1984- |e VerfasserIn |0 (DE-588)1072015560 |0 (DE-627)826782949 |0 (DE-576)433484144 |4 aut | |
| 245 | 1 | 0 | |a Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury |c Johannes Maximilian Ludwig, Yuling Zhang, Walee Chamulitrat, Wolfgang Stremmel, Anita Pathil |
| 264 | 1 | |c May 24, 2018 | |
| 300 | |a 15 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 01.08.2018 | ||
| 520 | |a Aim: Endotoxin-mediated liver inflammation is a key component of many acute and chronic liver diseases contributing to liver damage, fibrosis and eventually organ failure. Here, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate regarding its anti-inflammatory and anti-fibrogenic properties. Methods: Anti-inflammatory properties of UDCA-LPE were evaluated in a mouse model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced acute liver injury, LPS treated RAW264.7 macrophages and murine primary Kupffer cells. Furthermore, anti-inflammatory and anti-fibrotic effects of UDCA-LPE were studied on primary hepatic stellate cells (HSC) incubated with supernatant from LPS±UDCA-LPE treated RAW264.7 cells. Results: UDCA-LPE ameliorated LPS-induced increase of IL-6, TNF-α, TGF-β, NOX-2 in the GalN/LPS model by up to 80.2% for IL-6. Similarly, UDCA-LPE markedly decreased the expression of inflammatory cytokines IL-6, TNF-α and TGF-β as well as the chemokines MCP1 and RANTES in LPS-stimulated RAW 264.7 cells. Anti-inflammatory effects were also observed in primary murine Kupffer cells. Mechanistic evaluation revealed a reversion of LPS-activated pro-inflammatory TLR4 pathway by UDCA-LPE. Moreover, UDCA-LPE inhibited iNOS and NOX-2 expression while activating eNOS via phosphorylation of AKT and pERK1/2 in RAW264.7 cells. HSC treated with conditioned medium from LPS±UDCA-LPE RAW264.7 cells showed lower fibrogenic activation due to less SMAD2/3 phosphorylation, reduced expression of profibrogenic CTGF and reduced pro-inflammatory chemokine expression. Conclusion: In the setting of endotoxin-mediated liver inflammation, UDCA-LPE exerts profound anti-inflammatory and anti-fibrotic effect implying a promising potential for the drug candidate as an experimental approach for the treatment of acute and chronic liver diseases. | ||
| 650 | 4 | |a Acute liver failure | |
| 650 | 4 | |a Chemokines | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Inflammatory diseases | |
| 650 | 4 | |a Liver diseases | |
| 650 | 4 | |a Liver fibrosis | |
| 650 | 4 | |a Mouse models | |
| 650 | 4 | |a Nitric oxide | |
| 700 | 1 | |a Zhang, Yuling |d 1988- |e VerfasserIn |0 (DE-588)1194552102 |0 (DE-627)1676568247 |4 aut | |
| 700 | 1 | |a Chamulitrat, Walee |d 1959- |e VerfasserIn |0 (DE-588)1037336828 |0 (DE-627)755493915 |0 (DE-576)39134479X |4 aut | |
| 700 | 1 | |a Stremmel, Wolfgang |d 1952- |e VerfasserIn |0 (DE-588)142773638 |0 (DE-627)640118747 |0 (DE-576)33331560X |4 aut | |
| 700 | 1 | |a Pathil-Warth, Anita |d 1981- |e VerfasserIn |0 (DE-588)132644304 |0 (DE-627)524715890 |0 (DE-576)260118915 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PLOS ONE |d San Francisco, California, US : PLOS, 2006 |g 13(2018,5) Artikel-Nummer e0197836, 15 Seiten |h Online-Ressource |w (DE-627)523574592 |w (DE-600)2267670-3 |w (DE-576)281331979 |x 1932-6203 |7 nnas |a Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury |
| 773 | 1 | 8 | |g volume:13 |g year:2018 |g number:5 |g extent:15 |a Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0197836 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197836 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180801 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 132644304 |a Pathil-Warth, Anita |m 132644304:Pathil-Warth, Anita |d 910000 |d 910100 |e 910000PP132644304 |e 910100PP132644304 |k 0/910000/ |k 1/910000/910100/ |p 5 |y j | ||
| 998 | |g 142773638 |a Stremmel, Wolfgang |m 142773638:Stremmel, Wolfgang |d 910000 |d 910100 |e 910000PS142773638 |e 910100PS142773638 |k 0/910000/ |k 1/910000/910100/ |p 4 | ||
| 998 | |g 1037336828 |a Chamulitrat, Walee |m 1037336828:Chamulitrat, Walee |d 910000 |d 910100 |e 910000PC1037336828 |e 910100PC1037336828 |k 0/910000/ |k 1/910000/910100/ |p 3 | ||
| 998 | |g 1194552102 |a Zhang, Yuling |m 1194552102:Zhang, Yuling |d 910000 |d 910100 |e 910000PZ1194552102 |e 910100PZ1194552102 |k 0/910000/ |k 1/910000/910100/ |p 2 | ||
| 998 | |g 1072015560 |a Ludwig, Johannes Maximilian |m 1072015560:Ludwig, Johannes Maximilian |p 1 |x j | ||
| 999 | |a KXP-PPN1578163021 |e 3020039452 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"doi":["10.1371/journal.pone.0197836"],"eki":["1578163021"]},"type":{"media":"Online-Ressource","bibl":"article-journal"},"relHost":[{"name":{"displayForm":["Public Library of Science"]},"physDesc":[{"extent":"Online-Ressource"}],"disp":"Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injuryPLOS ONE","recId":"523574592","corporate":[{"display":"Public Library of Science","role":"isb","roleDisplay":"Herausgebendes Organ"}],"note":["Schreibweise des Titels bis 2012: PLoS ONE","Gesehen am 20.03.19"],"language":["eng"],"title":[{"title":"PLOS ONE","title_sort":"PLOS ONE"}],"id":{"zdb":["2267670-3"],"issn":["1932-6203"],"eki":["523574592"]},"origin":[{"dateIssuedDisp":"2006-","dateIssuedKey":"2006","publisherPlace":"San Francisco, California, US ; Lawrence, Kan.","publisher":"PLOS ; PLoS"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"part":{"year":"2018","extent":"15","volume":"13","text":"13(2018,5) Artikel-Nummer e0197836, 15 Seiten","issue":"5"},"pubHistory":["1.2006 -"]}],"origin":[{"dateIssuedDisp":"May 24, 2018","dateIssuedKey":"2018"}],"note":["Gesehen am 01.08.2018"],"recId":"1578163021","title":[{"title_sort":"Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury","title":"Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury"}],"language":["eng"],"physDesc":[{"extent":"15 S."}],"person":[{"given":"Johannes Maximilian","family":"Ludwig","display":"Ludwig, Johannes Maximilian","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","family":"Zhang","given":"Yuling","display":"Zhang, Yuling"},{"display":"Chamulitrat, Walee","given":"Walee","family":"Chamulitrat","roleDisplay":"VerfasserIn","role":"aut"},{"roleDisplay":"VerfasserIn","role":"aut","display":"Stremmel, Wolfgang","family":"Stremmel","given":"Wolfgang"},{"roleDisplay":"VerfasserIn","role":"aut","family":"Pathil-Warth","given":"Anita","display":"Pathil-Warth, Anita"}],"name":{"displayForm":["Johannes Maximilian Ludwig, Yuling Zhang, Walee Chamulitrat, Wolfgang Stremmel, Anita Pathil"]}} | ||
| SRT | |a LUDWIGJOHAANTIINFLAM2420 | ||