Abstract Aims This study aimed to determine whether heat‑killed Latilactobacillus curvatus K4G4 exerts anti‑inflammatory effects in vivo using a monosodium urate‑induced peritonitis mouse model, and to elucidate the underlying mechanisms with a focus on IL‑10-mediated regulation of NLRP3 inflammasome activation in macrophages. Methods and results C57BL/6J mice were fed K4G4‑supplemented diets for 2 weeks prior to monosodium urate challenge. K4G4 significantly reduced monosodium urate‑induced neutrophil infiltration and suppressed the expression of Il1b and Nlrp3 in peritoneal cells. Spleen IL‑10 levels were elevated in K4G4‑fed mice. In J774.1 cells, K4G4 pretreatment increased Il10 expression and IL‑10 secretion, and dose‑dependently inhibited LPS/nigericin‑induced IL‑1β production and LDH release. IL‑10 neutralization restored IL‑1β production, indicating IL-10-dependent suppression of inflammasome activation. K4G4 also inhibited the priming step by reducing LPS‑induced Il1b, Tnfa, and Nlrp3 transcription and suppressing NF‑κB nuclear translocation. Furthermore, K4G4 attenuated LPS/nigericin‑induced caspase‑1 activation, confirming inhibition of the activation step. Conclusions Heat-killed K4G4 suppresses MSU-induced peritonitis in vivo and is associated with inhibition of both the priming and activation steps of NLRP3 inflammasome signaling, potentially involving IL-10–dependent mechanisms.
YAMADA et al. (Tue,) studied this question.