Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells
The anti-hyperglycemic drug glibenclamide (Glb) might represent an interesting therapeutic option in human neurodegenerative diseases because of its anti-inflammatory activity and its ability to downregulate activation of the NLRP3 inflammasome. Bi-functionalized liposomes that can cross the blood–b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/11/1590 |
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| author | Roberta Mancuso Lorenzo Agostino Citterio Simone Agostini Ivana Marventano Francesca La Rosa Francesca Re Pierfausto Seneci Marina Saresella Mario Clerici |
| author_facet | Roberta Mancuso Lorenzo Agostino Citterio Simone Agostini Ivana Marventano Francesca La Rosa Francesca Re Pierfausto Seneci Marina Saresella Mario Clerici |
| author_sort | Roberta Mancuso |
| collection | DOAJ |
| description | The anti-hyperglycemic drug glibenclamide (Glb) might represent an interesting therapeutic option in human neurodegenerative diseases because of its anti-inflammatory activity and its ability to downregulate activation of the NLRP3 inflammasome. Bi-functionalized liposomes that can cross the blood–brain barrier (BBB) may be used to release Glb into the central nervous system (CNS), overcoming its poor solubility and bioavailability. Here, we analyzed in vitro the effect of Glb-loaded nanovectors (GNVs) and Glb itself on NLRP3 inflammasome activation using a lipopolysaccharide- and nigericine-activated THP-1 cell model. Apoptosis-associated speck-like protein containing a CARD (ASC) aggregation and NLRP3-related cytokine (IL-1β, caspase 1, and IL-18) production and gene expression, as well as the concentration of miR-223-3p and miR-7-1-5p, known to modulate the NLRP3 inflammasome, were evaluated in all conditions. Results showed that both GNVs and Glb reduced significantly ASC-speck oligomerization, transcription and translation of NLRP3, as well as the secretion of caspase 1 and IL-1β (<i>p</i> < 0.05 for all). Unexpectedly, GNVs/Glb significantly suppressed miR-223-3p and upregulated miR-7-1-5p expression (<i>p</i> < 0.01). These preliminary results thus suggest that GNVs, similarly to Glb, are able to dampen NLRP3 inflammasome activation, inflammatory cytokine release, and modulate miR-223-3p/miR-7-1-5p. Although the mechanisms underlying the complex relation among these elements remain to be further investigated, these results can open new roads to the use of GNVs as a novel strategy to reduce inflammasome activation in disease and rehabilitation. |
| first_indexed | 2024-03-09T16:32:24Z |
| format | Article |
| id | doaj.art-83e7acefbe9c41a59dedbefab4f41aa6 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T16:32:24Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-83e7acefbe9c41a59dedbefab4f41aa62023-11-24T15:00:25ZengMDPI AGPharmaceuticals1424-82472023-11-011611159010.3390/ph16111590Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 CellsRoberta Mancuso0Lorenzo Agostino Citterio1Simone Agostini2Ivana Marventano3Francesca La Rosa4Francesca Re5Pierfausto Seneci6Marina Saresella7Mario Clerici8IRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, 20854 Milan, ItalyDipartimento di Chimica, University of Milan, 20122 Milan, ItalyIRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Gnocchi—ONLUS, 20148 Milan, ItalyThe anti-hyperglycemic drug glibenclamide (Glb) might represent an interesting therapeutic option in human neurodegenerative diseases because of its anti-inflammatory activity and its ability to downregulate activation of the NLRP3 inflammasome. Bi-functionalized liposomes that can cross the blood–brain barrier (BBB) may be used to release Glb into the central nervous system (CNS), overcoming its poor solubility and bioavailability. Here, we analyzed in vitro the effect of Glb-loaded nanovectors (GNVs) and Glb itself on NLRP3 inflammasome activation using a lipopolysaccharide- and nigericine-activated THP-1 cell model. Apoptosis-associated speck-like protein containing a CARD (ASC) aggregation and NLRP3-related cytokine (IL-1β, caspase 1, and IL-18) production and gene expression, as well as the concentration of miR-223-3p and miR-7-1-5p, known to modulate the NLRP3 inflammasome, were evaluated in all conditions. Results showed that both GNVs and Glb reduced significantly ASC-speck oligomerization, transcription and translation of NLRP3, as well as the secretion of caspase 1 and IL-1β (<i>p</i> < 0.05 for all). Unexpectedly, GNVs/Glb significantly suppressed miR-223-3p and upregulated miR-7-1-5p expression (<i>p</i> < 0.01). These preliminary results thus suggest that GNVs, similarly to Glb, are able to dampen NLRP3 inflammasome activation, inflammatory cytokine release, and modulate miR-223-3p/miR-7-1-5p. Although the mechanisms underlying the complex relation among these elements remain to be further investigated, these results can open new roads to the use of GNVs as a novel strategy to reduce inflammasome activation in disease and rehabilitation.https://www.mdpi.com/1424-8247/16/11/1590glibenclamidenanoparticlesNLRP3 inflammasomemicroRNAsrehabilitation |
| spellingShingle | Roberta Mancuso Lorenzo Agostino Citterio Simone Agostini Ivana Marventano Francesca La Rosa Francesca Re Pierfausto Seneci Marina Saresella Mario Clerici Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells Pharmaceuticals glibenclamide nanoparticles NLRP3 inflammasome microRNAs rehabilitation |
| title | Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells |
| title_full | Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells |
| title_fullStr | Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells |
| title_full_unstemmed | Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells |
| title_short | Glibenclamide-Loaded Nanoparticles Reduce NLRP3 Inflammasome Activation and Modulate miR-223-3p/miR-7-1-5p Expression in THP-1 Cells |
| title_sort | glibenclamide loaded nanoparticles reduce nlrp3 inflammasome activation and modulate mir 223 3p mir 7 1 5p expression in thp 1 cells |
| topic | glibenclamide nanoparticles NLRP3 inflammasome microRNAs rehabilitation |
| url | https://www.mdpi.com/1424-8247/16/11/1590 |
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