Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Al-Dwairi A

PROVIDER: S-EPMC5865574 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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.

Al-Dwairi Ahmed A Alqudah Tamara E TE Al-Shboul Othman O Alqudah Mohammad M Mustafa Ayman G AG Alfaqih Mahmoud A MA

Journal of inflammation research 20180320

<h4>Background</h4>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.<h4>Ai ...[more]

PMID: 29593427

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Project description:Recently we discovered that intact kidneys release into the extracellular compartment 2',3'-cAMP (a positional isomer of 3',5'-cAMP with unknown pharmacology) and metabolize 2',3'-cAMP to 2'-AMP, 3'-AMP, and adenosine. Because adenosine inhibits growth of vascular smooth muscle cells and mesangial cells, we tested the hypothesis that extracellular 2',3'-cAMP attenuates growth of preglomerular vascular smooth muscle and mesangial cells via production of adenosine. For comparison, all of the experiments were performed with both 2',3'-cAMP and 3',5'-cAMP. In study 1, 2',3'-cAMP, 3',5'-cAMP, 5'-AMP, 3'-AMP, or 2'-AMP was incubated with cells and purines measured in the medium by mass spectrometry. Both preglomerular vascular smooth muscle and mesangial cells metabolized 3',5'-cAMP to 5'-AMP and adenosine; 5'-AMP to adenosine; 2',3'-cAMP to 2'-AMP, 3'-AMP, and adenosine; and 2'-AMP and 3'-AMP to adenosine. 3-Isobutyl-1-methylxanthine (phosphodiesterase inhibitor) and 1,3-dipropyl-8-p-sulfophenylxanthine (ecto-phosphodiesterase inhibitor) blocked conversion of 3',5'-cAMP to 5'-AMP and adenosine, and alpha,beta-methylene-adenosine-5'-diphosphate (CD73 inhibitor) blocked conversion of 5'-AMP to adenosine. These enzyme inhibitors had little effect on metabolism of 2',3'-cAMP, 2'-AMP, or 3'-AMP. For study 2, 2',3'-cAMP and 3',5'-cAMP profoundly inhibited proliferation (thymidine incorporation and cell number) of both cell types, with 2',3'-cAMP more potent than 3',5'-cAMP. Antagonism of A(2B) receptors (MRS-1724), but not A(1) (1,3-dipropyl-8-cyclopentylxanthine), A(2A) (SCH-58261), or A(3) (VUF-5574) receptors, attenuated the growth inhibitory effects of 2',3'-cAMP and 3',5'-cAMP. Extracellular 2',3'-cAMP inhibits growth of preglomerular vascular smooth muscle and mesangial cells more profoundly than does 3',5'-cAMP. Although both cAMPs inhibit growth in part via conversion to adenosine followed by A(2B) receptor activation, their metabolism is mediated by different enzymes.

Dataset Information

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.

Background

Aim

Materials and methods

Results

Conclusion

Publications

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.

Similar Datasets

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