Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells.
Dynorphin 1-17, (DYN 1-17) opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP) receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4824444?pdf=render |
id |
doaj-8a44de2463a34cd294ba459b456f43d5 |
---|---|
record_format |
Article |
spelling |
doaj-8a44de2463a34cd294ba459b456f43d52020-11-25T02:39:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015300510.1371/journal.pone.0153005Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells.Siti Sarah Fazalul RahimanMichael MorganPaul GrayPaul Nicholas ShawPeter John CabotDynorphin 1-17, (DYN 1-17) opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP) receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) from lipopolysaccharide (LPS)-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM). Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11) on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM). These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.http://europepmc.org/articles/PMC4824444?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siti Sarah Fazalul Rahiman Michael Morgan Paul Gray Paul Nicholas Shaw Peter John Cabot |
spellingShingle |
Siti Sarah Fazalul Rahiman Michael Morgan Paul Gray Paul Nicholas Shaw Peter John Cabot Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. PLoS ONE |
author_facet |
Siti Sarah Fazalul Rahiman Michael Morgan Paul Gray Paul Nicholas Shaw Peter John Cabot |
author_sort |
Siti Sarah Fazalul Rahiman |
title |
Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. |
title_short |
Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. |
title_full |
Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. |
title_fullStr |
Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. |
title_full_unstemmed |
Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells. |
title_sort |
dynorphin 1-17 and its n-terminal biotransformation fragments modulate lipopolysaccharide-stimulated nuclear factor-kappa b nuclear translocation, interleukin-1beta and tumor necrosis factor-alpha in differentiated thp-1 cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Dynorphin 1-17, (DYN 1-17) opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP) receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) from lipopolysaccharide (LPS)-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM). Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11) on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM). These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways. |
url |
http://europepmc.org/articles/PMC4824444?pdf=render |
work_keys_str_mv |
AT sitisarahfazalulrahiman dynorphin117anditsnterminalbiotransformationfragmentsmodulatelipopolysaccharidestimulatednuclearfactorkappabnucleartranslocationinterleukin1betaandtumornecrosisfactoralphaindifferentiatedthp1cells AT michaelmorgan dynorphin117anditsnterminalbiotransformationfragmentsmodulatelipopolysaccharidestimulatednuclearfactorkappabnucleartranslocationinterleukin1betaandtumornecrosisfactoralphaindifferentiatedthp1cells AT paulgray dynorphin117anditsnterminalbiotransformationfragmentsmodulatelipopolysaccharidestimulatednuclearfactorkappabnucleartranslocationinterleukin1betaandtumornecrosisfactoralphaindifferentiatedthp1cells AT paulnicholasshaw dynorphin117anditsnterminalbiotransformationfragmentsmodulatelipopolysaccharidestimulatednuclearfactorkappabnucleartranslocationinterleukin1betaandtumornecrosisfactoralphaindifferentiatedthp1cells AT peterjohncabot dynorphin117anditsnterminalbiotransformationfragmentsmodulatelipopolysaccharidestimulatednuclearfactorkappabnucleartranslocationinterleukin1betaandtumornecrosisfactoralphaindifferentiatedthp1cells |
_version_ |
1724783685936349184 |