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Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells

BACKGROUND: Gastric injury is the most common digestive system disease worldwide and involves inflammation, which can lead to gastric ulcer or gastric cancer (GC). Matrix metallopeptidase-9 [MMP-9 (gelatinase-B)] plays an important role in inflammation and GC progression. Quercetin and quercetin-ric...

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Autores principales: Hsieh, Hsi-Lung, Yu, Ming-Chin, Cheng, Li-Ching, Chu, Mei-Yi, Huang, Tzu-Hao, Yeh, Ta-Sen, Tsai, Ming-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985486/
https://www.ncbi.nlm.nih.gov/pubmed/35431500
http://dx.doi.org/10.3748/wjg.v28.i11.1139
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author Hsieh, Hsi-Lung
Yu, Ming-Chin
Cheng, Li-Ching
Chu, Mei-Yi
Huang, Tzu-Hao
Yeh, Ta-Sen
Tsai, Ming-Ming
author_facet Hsieh, Hsi-Lung
Yu, Ming-Chin
Cheng, Li-Ching
Chu, Mei-Yi
Huang, Tzu-Hao
Yeh, Ta-Sen
Tsai, Ming-Ming
author_sort Hsieh, Hsi-Lung
collection PubMed
description BACKGROUND: Gastric injury is the most common digestive system disease worldwide and involves inflammation, which can lead to gastric ulcer or gastric cancer (GC). Matrix metallopeptidase-9 [MMP-9 (gelatinase-B)] plays an important role in inflammation and GC progression. Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities. However, the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear. AIM: To assess whether tumor necrosis factor-α (TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells. METHODS: The normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the anti-inflammatory effects of quercetin. The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line. Cell migration was measured using Transwell assay. The expression of proto-oncogene tyrosine-protein kinase Src (c-Src), phospho (p)-c-Src, extracellular-signal-regulated kinase 2 (ERK2), p-ERK1/2, c-Fos, p-c-Fos, nuclear factor kappa B (NF-κB/p65), and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity. p65 expression was detected by immunofluorescence. MMP-9 mRNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction (qRT–PCR) and gelatin zymography, respectively. RESULTS: qRT-PCR and gelatin zymography showed that TNF-α induced MMP-9 mRNA and protein expression in a dose- and time-dependent manner. These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-α antagonist (TNFR inhibitor) in a dose- and time-dependent manner. Quercetin and TNF-α antagonists decreased the TNF-α-induced phosphorylation of c-Src, ERK1/2, c-Fos, and p65 in a dose- and time-dependent manner. Quercetin, TNF-α antagonist, PP1, U0126, and tanshinone IIA (TSIIA) reduced TNF-α-induced c-Fos phosphorylation and AP-1–Luciferase (Luc) activity in a dose- and time-dependent manner. Pretreatment with quercetin, TNF-α antagonist, PP1, U0126, or Bay 11-7082 reduced TNF-α-induced p65 phosphorylation and translocation and p65–Luc activity in a dose- and time-dependent manner. TNF-α significantly increased GES-1 cell migration, and these results were reduced by pretreatment with quercetin or a TNF-α antagonist. CONCLUSION: Quercetin significantly downregulates TNF-α-induced MMP-9 expression in GES-1 cells via the TNFR-c-Src–ERK1/2 and c-Fos or NF-κB pathways.
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spelling pubmed-89854862022-04-15 Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells Hsieh, Hsi-Lung Yu, Ming-Chin Cheng, Li-Ching Chu, Mei-Yi Huang, Tzu-Hao Yeh, Ta-Sen Tsai, Ming-Ming World J Gastroenterol Basic Study BACKGROUND: Gastric injury is the most common digestive system disease worldwide and involves inflammation, which can lead to gastric ulcer or gastric cancer (GC). Matrix metallopeptidase-9 [MMP-9 (gelatinase-B)] plays an important role in inflammation and GC progression. Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities. However, the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear. AIM: To assess whether tumor necrosis factor-α (TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells. METHODS: The normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the anti-inflammatory effects of quercetin. The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line. Cell migration was measured using Transwell assay. The expression of proto-oncogene tyrosine-protein kinase Src (c-Src), phospho (p)-c-Src, extracellular-signal-regulated kinase 2 (ERK2), p-ERK1/2, c-Fos, p-c-Fos, nuclear factor kappa B (NF-κB/p65), and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity. p65 expression was detected by immunofluorescence. MMP-9 mRNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction (qRT–PCR) and gelatin zymography, respectively. RESULTS: qRT-PCR and gelatin zymography showed that TNF-α induced MMP-9 mRNA and protein expression in a dose- and time-dependent manner. These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-α antagonist (TNFR inhibitor) in a dose- and time-dependent manner. Quercetin and TNF-α antagonists decreased the TNF-α-induced phosphorylation of c-Src, ERK1/2, c-Fos, and p65 in a dose- and time-dependent manner. Quercetin, TNF-α antagonist, PP1, U0126, and tanshinone IIA (TSIIA) reduced TNF-α-induced c-Fos phosphorylation and AP-1–Luciferase (Luc) activity in a dose- and time-dependent manner. Pretreatment with quercetin, TNF-α antagonist, PP1, U0126, or Bay 11-7082 reduced TNF-α-induced p65 phosphorylation and translocation and p65–Luc activity in a dose- and time-dependent manner. TNF-α significantly increased GES-1 cell migration, and these results were reduced by pretreatment with quercetin or a TNF-α antagonist. CONCLUSION: Quercetin significantly downregulates TNF-α-induced MMP-9 expression in GES-1 cells via the TNFR-c-Src–ERK1/2 and c-Fos or NF-κB pathways. Baishideng Publishing Group Inc 2022-03-21 2022-03-21 /pmc/articles/PMC8985486/ /pubmed/35431500 http://dx.doi.org/10.3748/wjg.v28.i11.1139 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Basic Study
Hsieh, Hsi-Lung
Yu, Ming-Chin
Cheng, Li-Ching
Chu, Mei-Yi
Huang, Tzu-Hao
Yeh, Ta-Sen
Tsai, Ming-Ming
Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
title Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
title_full Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
title_fullStr Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
title_full_unstemmed Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
title_short Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
title_sort quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985486/
https://www.ncbi.nlm.nih.gov/pubmed/35431500
http://dx.doi.org/10.3748/wjg.v28.i11.1139
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