The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models

While the beneficial effects of colchicine on inflammation and infarcted myocardium have been documented, its impact on cardiac fibroblast activation in the context of myocardial infarction (MI) remains unknown. This study aimed to investigate the effect of colchicine on the regulation of NOD-like r...

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Main Authors: Tri Astiawati, Mohammad Saifur Rohman, Titin Wihastuti, Hidayat Sujuti, Agustina Endharti, Djanggan Sargowo, Delvac Oceandy, Bayu Lestari, Efta Triastuti, Ricardo Adrian Nugraha
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Language:English
Published: MDPI AG 2025-03-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/3/367
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author Tri Astiawati
Mohammad Saifur Rohman
Titin Wihastuti
Hidayat Sujuti
Agustina Endharti
Djanggan Sargowo
Delvac Oceandy
Bayu Lestari
Efta Triastuti
Ricardo Adrian Nugraha
author_facet Tri Astiawati
Mohammad Saifur Rohman
Titin Wihastuti
Hidayat Sujuti
Agustina Endharti
Djanggan Sargowo
Delvac Oceandy
Bayu Lestari
Efta Triastuti
Ricardo Adrian Nugraha
author_sort Tri Astiawati
collection DOAJ
description While the beneficial effects of colchicine on inflammation and infarcted myocardium have been documented, its impact on cardiac fibroblast activation in the context of myocardial infarction (MI) remains unknown. This study aimed to investigate the effect of colchicine on the regulation of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and Interleukin-1β (IL-1β) expression in fibroblasts. 3T3 fibroblasts were exposed to 600 μM CoCl<sub>2</sub> for 24 h to simulate hypoxia, with normoxic cells as controls. Colchicine (1 μM) was administered for 24 h. ASC-NLRP3 colocalization and IL-1β expression were evaluated using immunofluorescence and flow cytometry, respectively. Data were analyzed using t-tests and one-way ANOVA with post hoc tests. Hypoxia treatment significantly induced apoptosis-associated speck-like protein containing a CARD (ASC)-NLRP3 colocalization (<i>p</i> < 0.05). Colchicine treatment of hypoxic 3T3 cells reduced ASC-NLRP3 colocalization, although this reduction was not statistically significant. Additionally, IL-1β expression was significantly inhibited in colchicine-treated hypoxic 3T3 cells compared to those treated with placebo (<i>p</i> < 0.05). The findings of this study indicate that colchicine treatment inhibits the activation of the NLRP3 inflammasome by disrupting the colocalization of ASC and NLRP3, thereby reducing IL-1β expression in CoCl<sub>2</sub>-treated 3T3 cells.
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spelling doaj-art-ff914e26613046e397bd35d280cabdf12025-08-20T02:11:22ZengMDPI AGBiomolecules2218-273X2025-03-0115336710.3390/biom15030367The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro ModelsTri Astiawati0Mohammad Saifur Rohman1Titin Wihastuti2Hidayat Sujuti3Agustina Endharti4Djanggan Sargowo5Delvac Oceandy6Bayu Lestari7Efta Triastuti8Ricardo Adrian Nugraha9Doctoral Program of Medical Science, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDepartment of Cardiology and Cardiovascular Medicine, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDepartment of Biomedical, Nursing Science, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDepartment of Biochemistry, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDoctoral Program of Medical Science, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDepartment of Cardiology and Vascular Medicine, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDivision of Cardiovascular Science, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKDepartment of Pharmacology, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UKDepartment of Pharmacy, Faculty of Medicine, Brawijaya University, Malang 65145, IndonesiaDepartment of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga—Dr. Soetomo General Academic Hospital, Surabaya 60286, IndonesiaWhile the beneficial effects of colchicine on inflammation and infarcted myocardium have been documented, its impact on cardiac fibroblast activation in the context of myocardial infarction (MI) remains unknown. This study aimed to investigate the effect of colchicine on the regulation of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and Interleukin-1β (IL-1β) expression in fibroblasts. 3T3 fibroblasts were exposed to 600 μM CoCl<sub>2</sub> for 24 h to simulate hypoxia, with normoxic cells as controls. Colchicine (1 μM) was administered for 24 h. ASC-NLRP3 colocalization and IL-1β expression were evaluated using immunofluorescence and flow cytometry, respectively. Data were analyzed using t-tests and one-way ANOVA with post hoc tests. Hypoxia treatment significantly induced apoptosis-associated speck-like protein containing a CARD (ASC)-NLRP3 colocalization (<i>p</i> < 0.05). Colchicine treatment of hypoxic 3T3 cells reduced ASC-NLRP3 colocalization, although this reduction was not statistically significant. Additionally, IL-1β expression was significantly inhibited in colchicine-treated hypoxic 3T3 cells compared to those treated with placebo (<i>p</i> < 0.05). The findings of this study indicate that colchicine treatment inhibits the activation of the NLRP3 inflammasome by disrupting the colocalization of ASC and NLRP3, thereby reducing IL-1β expression in CoCl<sub>2</sub>-treated 3T3 cells.https://www.mdpi.com/2218-273X/15/3/367ASC-NLRP3inflammasomecolchicineIL-1βischemia
spellingShingle Tri Astiawati
Mohammad Saifur Rohman
Titin Wihastuti
Hidayat Sujuti
Agustina Endharti
Djanggan Sargowo
Delvac Oceandy
Bayu Lestari
Efta Triastuti
Ricardo Adrian Nugraha
The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models
Biomolecules
ASC-NLRP3
inflammasome
colchicine
IL-1β
ischemia
title The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models
title_full The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models
title_fullStr The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models
title_full_unstemmed The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models
title_short The Emerging Role of Colchicine to Inhibit NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models
title_sort emerging role of colchicine to inhibit nod like receptor family pyrin domain containing 3 inflammasome and interleukin 1β expression in in vitro models
topic ASC-NLRP3
inflammasome
colchicine
IL-1β
ischemia
url https://www.mdpi.com/2218-273X/15/3/367
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