Version 1
: Received: 12 January 2024 / Approved: 13 January 2024 / Online: 15 January 2024 (03:18:45 CET)
How to cite:
Kim, S.-K.; Choe, J.-Y.; Kim, J.-W.; Park, K.-Y.; Kim, B. Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation. Preprints2024, 2024011062. https://doi.org/10.20944/preprints202401.1062.v1
Kim, S.-K.; Choe, J.-Y.; Kim, J.-W.; Park, K.-Y.; Kim, B. Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation. Preprints 2024, 2024011062. https://doi.org/10.20944/preprints202401.1062.v1
Kim, S.-K.; Choe, J.-Y.; Kim, J.-W.; Park, K.-Y.; Kim, B. Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation. Preprints2024, 2024011062. https://doi.org/10.20944/preprints202401.1062.v1
APA Style
Kim, S. K., Choe, J. Y., Kim, J. W., Park, K. Y., & Kim, B. (2024). Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation. Preprints. https://doi.org/10.20944/preprints202401.1062.v1
Chicago/Turabian Style
Kim, S., Ki-Yeun Park and Boyoung Kim. 2024 "Anti-inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3 Complex Activation" Preprints. https://doi.org/10.20944/preprints202401.1062.v1
Abstract
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.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
