Permalink : http://hdl.handle.net/2115/82757

KEYWORDS : Toll like receptor 2;nterleukin-1β;mycoplasmal lipoprotein;FSL-1;NLRP3 inflammasome

The proinflammatory cytokine interleukin (IL)- 1β plays a crucial role in controlling bacterial infections and is produced after the processing of pro-IL- 1β by caspase-1, which is activated by the inflammasome. Mycoplasmal membrane lipoprotein and lipopeptide, which are typical Toll-like receptor 2 (TLR2) ligands, activate the NLRP3 inflammasome to produce IL-1β in macrophages, although the molecular mechanism behind this remains unclear. Here, we found that lipoproteins from Mycoplasma salivarium (MsLP) and M. pneumoniae (MpLP) and an M. salivarium-derived lipopeptide (FSL-1) exhibited IL-1β-inducing activity toward bone marrow-derived macrophages from C57BL/6 mice (TLR2+/+ BMMs), whereas the activity toward BMMs from TLR2-deficient mice (TLR2－/－ BMMs) was markedly reduced. Microarray analysis suggested that FSL-1 upregulates the potassium voltage-gated channel, subfamily F, member 1 (Kcnf1), which is involved in K+ efflux as one of the NLRP3 inflammasome activators, in a TLR2-dependent manner. Moreover, we found that a high extracellular concentration of K+, which blocks K+ efflux, downregulated the release of IL-1β. Thus, this study is the first to suggest that TLR2-mediated signals triggered by mycoplasmal lipoproteins/lipopeptide upregulate potassium channels to promote K+ efflux, by which the NLRP3 inflammasome is activated.