title: Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation.
abstract: 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.
authors.affiliation: College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
authors.forename: Huijeong
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
authors.forename: Seung Goo
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Yoon
authors.affiliation: Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
authors.forename: Pyeung-Hyeun
authors.initials: PH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
authors.forename: Doo
authors.initials: D
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
authors.forename: Geun-Shik
authors.initials: GS
authors.lastname: Lee
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001412:Bacillus subtilis / Q000737:chemistry*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013025:Glycine max; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C540422:Aim2 protein, mouse; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D018836:Inflammation Mediators; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051197:Toll-Like Receptor 4; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D018698:Glutamic Acid; D020170:Caspase 1