Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro

Ahmed Al-Dwairi,1 Tamara E Alqudah,1 Othman Al-Shboul,1 Mohammad Alqudah,1 Ayman G Mustafa,2 Mahmoud A Alfaqih1 1Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Anatomy, Faculty of Medicine, Jordan University...

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Autores principales: Al-Dwairi A, Alqudah TE, Al-Shboul O, Alqudah M, Mustafa AG, Alfaqih MA
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Lenguaje:EN
Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:a79a71c25a0e404f932e11d38d48037c2021-12-02T07:29:50ZGlucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro1178-7031https://doaj.org/article/a79a71c25a0e404f932e11d38d48037c2018-03-01T00:00:00Zhttps://www.dovepress.com/glucagon-like-peptide-1-exerts-anti-inflammatory-effects-on-mouse-colo-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Ahmed Al-Dwairi,1 Tamara E Alqudah,1 Othman Al-Shboul,1 Mohammad Alqudah,1 Ayman G Mustafa,2 Mahmoud A Alfaqih1 1Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan Background: Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. Aim: The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS). Materials and methods: Freshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 µg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane. Results: CSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly (p<0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation. Conclusion: These data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions. Keywords: GLP-1, inflammation, inflammatory bowel disease, smooth muscleAl-Dwairi AAlqudah TEAl-Shboul OAlqudah MMustafa AGAlfaqih MADove Medical PressarticleGLP-1inflammationIBDSmooth muscle.PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 95-109 (2018)
institution DOAJ
collection DOAJ
language EN
topic GLP-1
inflammation
IBD
Smooth muscle.
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle GLP-1
inflammation
IBD
Smooth muscle.
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Al-Dwairi A
Alqudah TE
Al-Shboul O
Alqudah M
Mustafa AG
Alfaqih MA
Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro
description Ahmed Al-Dwairi,1 Tamara E Alqudah,1 Othman Al-Shboul,1 Mohammad Alqudah,1 Ayman G Mustafa,2 Mahmoud A Alfaqih1 1Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan Background: Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. Aim: The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS). Materials and methods: Freshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 µg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane. Results: CSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly (p<0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation. Conclusion: These data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions. Keywords: GLP-1, inflammation, inflammatory bowel disease, smooth muscle
format article
author Al-Dwairi A
Alqudah TE
Al-Shboul O
Alqudah M
Mustafa AG
Alfaqih MA
author_facet Al-Dwairi A
Alqudah TE
Al-Shboul O
Alqudah M
Mustafa AG
Alfaqih MA
author_sort Al-Dwairi A
title Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro
title_short Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro
title_full Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro
title_fullStr Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro
title_full_unstemmed Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro
title_sort glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κb pathway in vitro
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/a79a71c25a0e404f932e11d38d48037c
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