Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4...

Poly-gamma-glutamic acid (γ-PGA) is a natural, edible and non-toxic polymer synthesized by Bacillus subtilis and is suggested as a safe biomaterial for the use in hydrogels and vaccine adjuvants. However, the effect of γ-PGA on inflammasome activation has not yet been studied in macrophages. Inflammasomes, which are intracellular multi-protein complexes, promote acute and chronic inflammation via interleukin-1β or interleukin-18 maturation, and they are known targets for metabolic syndromes and cancer. In this study, we observed that γ-PGA attenuated NLRP3, NLRC4 and AIM2 inflammasome activation, whereas it upregulated pro-inflammatory cytokine expression in human and murine macrophages. Although γ-PGA had conflicting effects on cytokine production and maturation, it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal model. Thus, we suggest γ-PGA as a candidate to control inflammasome-mediated disorders.