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Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production

We screened 57 chemical probes, high-quality tool compounds, and relevant clinically used drugs to investigate their effect on pro-inflammatory prostaglandin E(2) (PGE(2)) production and interleukin-8 (IL-8) secretion in human whole blood. Freshly drawn blood from healthy volunteers and patients wit...

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Autores principales: Bergqvist, Filip, Sundström, Yvonne, Shang, Ming-Mei, Gunnarsson, Iva, Lundberg, Ingrid E., Sundström, Michael, Jakobsson, Per-Johan, Berg, Louise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218097/
https://www.ncbi.nlm.nih.gov/pubmed/32435199
http://dx.doi.org/10.3389/fphar.2020.00613
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author Bergqvist, Filip
Sundström, Yvonne
Shang, Ming-Mei
Gunnarsson, Iva
Lundberg, Ingrid E.
Sundström, Michael
Jakobsson, Per-Johan
Berg, Louise
author_facet Bergqvist, Filip
Sundström, Yvonne
Shang, Ming-Mei
Gunnarsson, Iva
Lundberg, Ingrid E.
Sundström, Michael
Jakobsson, Per-Johan
Berg, Louise
author_sort Bergqvist, Filip
collection PubMed
description We screened 57 chemical probes, high-quality tool compounds, and relevant clinically used drugs to investigate their effect on pro-inflammatory prostaglandin E(2) (PGE(2)) production and interleukin-8 (IL-8) secretion in human whole blood. Freshly drawn blood from healthy volunteers and patients with systemic lupus erythematosus (SLE) or dermatomyositis was incubated with compounds at 0.1 or 1 µM and treated with lipopolysaccharide (LPS, 10 µg/ml) to induce a pro-inflammatory condition. Plasma was collected after 24 h for lipid profiling using liquid chromatography tandem mass spectrometry (LC-MS/MS) and IL-8 quantification using enzyme-linked immunosorbent assay (ELISA). Each compound was tested in at least four donors at one concentration based on prior knowledge of binding affinities and in vitro activity. Our screening suggested that PD0325901 (MEK-1/2 inhibitor), trametinib (MEK-1/2 inhibitor), and selumetinib (MEK-1 inhibitor) decreased while tofacitinib (JAK inhibitor) increased PGE(2) production. These findings were validated by concentration–response experiment in two donors. Moreover, the tested MEK inhibitors decreased thromboxane B(2) (TXB(2)) production and IL-8 secretion. We also investigated the lysophophatidylcholine (LPC) profile in plasma from treated whole blood as these lipids are potentially important mediators in inflammation, and we did not observe any changes in LPC profiles. Collectively, we deployed a semi-high throughput and robust methodology to investigate anti-inflammatory properties of new chemical probes.
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spelling pubmed-72180972020-05-20 Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production Bergqvist, Filip Sundström, Yvonne Shang, Ming-Mei Gunnarsson, Iva Lundberg, Ingrid E. Sundström, Michael Jakobsson, Per-Johan Berg, Louise Front Pharmacol Pharmacology We screened 57 chemical probes, high-quality tool compounds, and relevant clinically used drugs to investigate their effect on pro-inflammatory prostaglandin E(2) (PGE(2)) production and interleukin-8 (IL-8) secretion in human whole blood. Freshly drawn blood from healthy volunteers and patients with systemic lupus erythematosus (SLE) or dermatomyositis was incubated with compounds at 0.1 or 1 µM and treated with lipopolysaccharide (LPS, 10 µg/ml) to induce a pro-inflammatory condition. Plasma was collected after 24 h for lipid profiling using liquid chromatography tandem mass spectrometry (LC-MS/MS) and IL-8 quantification using enzyme-linked immunosorbent assay (ELISA). Each compound was tested in at least four donors at one concentration based on prior knowledge of binding affinities and in vitro activity. Our screening suggested that PD0325901 (MEK-1/2 inhibitor), trametinib (MEK-1/2 inhibitor), and selumetinib (MEK-1 inhibitor) decreased while tofacitinib (JAK inhibitor) increased PGE(2) production. These findings were validated by concentration–response experiment in two donors. Moreover, the tested MEK inhibitors decreased thromboxane B(2) (TXB(2)) production and IL-8 secretion. We also investigated the lysophophatidylcholine (LPC) profile in plasma from treated whole blood as these lipids are potentially important mediators in inflammation, and we did not observe any changes in LPC profiles. Collectively, we deployed a semi-high throughput and robust methodology to investigate anti-inflammatory properties of new chemical probes. Frontiers Media S.A. 2020-05-06 /pmc/articles/PMC7218097/ /pubmed/32435199 http://dx.doi.org/10.3389/fphar.2020.00613 Text en Copyright © 2020 Bergqvist, Sundström, Shang, Gunnarsson, Lundberg, Sundström, Jakobsson and Berg http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Bergqvist, Filip
Sundström, Yvonne
Shang, Ming-Mei
Gunnarsson, Iva
Lundberg, Ingrid E.
Sundström, Michael
Jakobsson, Per-Johan
Berg, Louise
Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production
title Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production
title_full Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production
title_fullStr Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production
title_full_unstemmed Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production
title_short Anti-Inflammatory Properties of Chemical Probes in Human Whole Blood: Focus on Prostaglandin E(2) Production
title_sort anti-inflammatory properties of chemical probes in human whole blood: focus on prostaglandin e(2) production
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218097/
https://www.ncbi.nlm.nih.gov/pubmed/32435199
http://dx.doi.org/10.3389/fphar.2020.00613
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