Shiitake mushroom-derived exosome-like nanoparticles (S-ELNs) suppressed nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome activity and interleukin (IL)-6 release. Bone marrow-derived macrophages (BMDMs) were preincubated with S-ELNs for 16 h, then treated with lipopolysaccharide (LPS) and free fatty acid (FFA) to activate the NLRP3 inflammasome. The cell-free culture medium was used to assess the levels of cytokines, including IL-1β (A), IL-18 (B), IL-6 (D), and tumor necrosis factor α (TNFα) (E), and lactate dehydrogenase (LDH) release (C). * p < 0.05, ** p < 0.01 relative to cells treated with LPS+FFA (black bar). The cell lysate was subjected to immunoblot analysis to measure the level of Caspase 1 (Casp1) p10 (Casp1 autocleavage product) when the NLRP3 and Absent in Melanoma 2 (AIM2) inflammasome were activated by LPS+FFA and LPS+DNA, respectively. (F). Tubulin is a loading control.