Response to Letter Regarding Article, "Anti-inflammatory and Antiatherogenic Effects of the Inflammasome NLRP3 Inhibitor Arglabin in ApoE2.Ki Mice Fed a High-Fat Diet".

In response to the letter of Drs Takahashi and Karasawa, we thought it might be of interest to open the debate about the mechanism by which arglabin, a natural compound isolated from Artemisia glabella , inhibits cholesterol crystal–induced activation of the NLRP3 inflammasome in murine macrophages. In the March 2015 online issue of Circulation 1 we evaluated the impact of arglabin on cholesterol crystal–mediated NLRP3 activation in cultured murine macrophages and in ApoE2.Ki mice fed a high-fat diet.We showed that both Nlrp3 knockout and inhibition of NLRP3 activation by the compound arglabin significantly decreased the size of atherosclerotic lesions in ApoE2.Ki mice fed a high-fat diet. At the molecular level, arglabin inhibited the activity of the NLRP3 inflammasome and significantly reduced the subsequent production of interleukin 1β (IL-1β) and interleukin 18 in vitro …