3-Hydroxyl-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitor (Statin)-induced 28-kDa Interleukin-1β Interferes with Mature IL-1β Signaling

Abstract

Background: HMG-CoA reductase inhibitors (statins) have anti-inflammatory effects, the molecular mechanisms of which remain unclear. Results: Statin treatment of macrophages induces secretion of a 28-kDa form of IL-1␤ that interferes with mature IL-1␤ signaling. Conclusion: Statins may dampen inflammation through induction of an anti-inflammatory form of IL-1␤. Significance: These observations may provide clues toward elucidating the in vivo anti-inflammatory effects of statins.

Inflammation in arterial diseases

“…Statins have been suggested for implementing CV prevention in systemic inflammatory conditions , whereas anti‐inflammatory effects of statins have been documented in large randomized clinical trial including MRC/BHF Heart Protection Study, TNT, AFCAPS/TexCAPS, WOSCOPS and JUPITER. Finally, more recent studies validated such results in smaller subpopulation .…”

A Fluorescent Reporter Mouse for Inflammasome Assembly Demonstrates an Important Role for Cell-Bound and Free ASC Specks during In Vivo Infection

“…Cells were transfected with poly(dA:dT) DNA through the use of Lipofectamine 2000 at a concentration of 1.5 μg/ml. IL-1β p17 and caspase-1 p20 immunoblots were conducted as described (Davaro et al, 2014) with antibodies from Adipogen (caspase-1 p20) and R&D Systems (IL-1β). The antibodies against β-actin were from Sigma.…”

Is immunity a mechanism contributing to statin-induced diabetes?

“…Statin-mediated inhibition of HMGCR, decreased mevalonate pathway intermediates and reduced protein prenylation may be a critical link, since addition of GGPP to statin-treated culture has been shown to restore ATP levels and inhibit IL-1b release. 17,20,56,59 However, it is not clear which prenylated protein(s) is/are involved. Three distinct prenyltransferases (Farnesyltransferase, FTase; Geranylgeranyltransferase I and II, GGTase-I and GGTase-II) are responsible for prenylation of an array of proteins including Ras, Rho and Rab family proteins.…”

“…In addition to statins and other NLRP3 inflammasome activators that are known to increase levels of (17 kDa) biologically active IL-1b, simvastatin and cerivastatin have recently been shown to processes pro-IL-1b to a 28 kDa intermediate form of IL-1b through a caspase-1-independent mechanism in macrophages. 59 IL-1b it is not the only candidate that could link the NLRP3 inflammasome to insulin action. The NLRP3 inflammasome also regulates biologically active IL-18.…”