Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation
Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. 
 Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of target molecules IL-1b, IL-37, caspase-1, and Smad3 was measured in THP-1 cells stimulated with MSU, atorvastatin, or rosuvastatin using real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1b or Smad3 siRNA in THP-1 cells was used to verify the pharmaceutical effect of statins in uric acid-induced inflammation.
 Results: Serum IL-37 level in gout patients was significantly higher than in controls (p < 0.001) and was associated with serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and transition of IL-37 from cytoplasm to nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1b in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1b expression but augmented translocation of IL-37 from cytoplasm to nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from cytoplasm to nucleus in THP-1 cells transfected with Smad3 siRNA compared to cells with negative control siRNA. 
 Conclusion: This study revealed that statins inhibit MSU-induced inflammatory response through augmentation of phosphorylated Smad3-mediated IL-37 expression in THP-1 cells..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Preprints.org - (2024) vom: 15. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Seong-Kyu [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.20944/preprints202401.1062.v1 |
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| PPN (Katalog-ID): |
preprintsorg042160685 |
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| 100 | 1 | |a Kim, Seong-Kyu |e verfasserin |0 (orcid)0000-0002-7780-0167 |4 aut | |
| 245 | 1 | 0 | |a Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation |
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| 520 | |a Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. 
 Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of target molecules IL-1b, IL-37, caspase-1, and Smad3 was measured in THP-1 cells stimulated with MSU, atorvastatin, or rosuvastatin using real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1b or Smad3 siRNA in THP-1 cells was used to verify the pharmaceutical effect of statins in uric acid-induced inflammation.
 Results: Serum IL-37 level in gout patients was significantly higher than in controls (p < 0.001) and was associated with serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and transition of IL-37 from cytoplasm to nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1b in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1b expression but augmented translocation of IL-37 from cytoplasm to nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from cytoplasm to nucleus in THP-1 cells transfected with Smad3 siRNA compared to cells with negative control siRNA. 
 Conclusion: This study revealed that statins inhibit MSU-induced inflammatory response through augmentation of phosphorylated Smad3-mediated IL-37 expression in THP-1 cells. | ||
| 700 | 1 | |a Choe, Jung-Yoon |4 aut | |
| 700 | 1 | |a Kim, Ji-Won |0 (orcid)0000-0002-0498-5762 |4 aut | |
| 700 | 1 | |a Park, Ki-Yeun |4 aut | |
| 700 | 1 | |a Kim, Boyoung |4 aut | |
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