Ursodeoxycholyl lysophosphatidylethanolamide negatively regulates TLR-mediated lipopolysaccharide response in human THP-1-derived macrophages

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F18%3A10383215" target="_blank" >RIV/00216208:11160/18:10383215 - isvavai.cz</a>

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0014299918301079" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0014299918301079</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2018.02.030" target="_blank" >10.1016/j.ejphar.2018.02.030</a>

Result language

angličtina

Original language name

Ursodeoxycholyl lysophosphatidylethanolamide negatively regulates TLR-mediated lipopolysaccharide response in human THP-1-derived macrophages

Original language description

The bile acid-phospholipid conjugate ursodeoxycholyl oleoyl-lysophophatidylethanolamide (UDCA-18:1LPE) is an anti-inflammatory and anti-fibrotic agent as previously shown in cultured hepatocytes and hepatic stellate cells as well as in in vivo models of liver injury. We hypothesize that UDCA-18:1LPE may directly inhibit the activation of immune cells. We found that UDCA-18:1LPE was capable of inhibiting the migration of phorbol ester-differentiated human THP-1 cells. We examined anti-inflammatory activity of UDCA-18:1LPE during activation of THP1-derived macrophages. Treatment of these macrophages by bacterial lipopolysaccharide (LPS) for 24 h induced the release of pro-inflammatory cytokines TNF-alpha, IL-6 and IL-1 beta. This release was markedly inhibited by pretreatment with UDCA-18:1LPE by similar to 65-90%. Derivatives with a different fatty-acid chain in LPE moiety also exhibited anti-inflammatory property. Western blotting and indirect immunofluorescence analyses revealed that UDCA-18:1LPE attenuated the expression of phosphorylated p38, MKK4/MKK7, JNK1/2, and c-Jun as well as nuclear translocation of NF-kappa B by similar to 22-86%. After LPS stimulation, the Toll-like receptor adaptor proteins, myeloid differentiation factor 88 and TNF receptor associated factor 6, were recruited into lipid rafts and UDCA-18:1LPE inhibited this recruitment by 22% and 58%, respectively. Moreover, LPS treatment caused a decrease of the known cytoprotective lysophosphatidylcholine species containing polyunsaturated fatty acids by 43%, and UDCA-18:1LPE co-treatment reversed this decrease. In conclusion, UDCA-18:1LPE and derivatives inhibited LPS inflammatory response by interfering with Toll-like receptor signaling in lipid rafts leading to an inhibition of MAPK and NF-kappa B activation. These conjugates may represent a class of lead compounds for development of anti-inflammatory drugs.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centre of drug-dietary supplements interactions and nutrigenetics</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

—

Volume of the periodical

825

Issue of the periodical within the volume

April

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

12

Pages from-to

63-74

UT code for WoS article

000427798900009

EID of the result in the Scopus database

2-s2.0-85042494432