Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

Huijeong Ahn; Seung Goo Kang; Sung-Il Yoon; Pyeung-Hyeun Kim; Doo Kim; Geun-Shik Lee

doi:10.1038/cmi.2016.13

Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation

Cell Mol Immunol. 2018 Feb;15(2):111-119. doi: 10.1038/cmi.2016.13. Epub 2016 May 2.

Authors

Huijeong Ahn¹, Seung Goo Kang², Sung-Il Yoon², Pyeung-Hyeun Kim³, Doo Kim¹, Geun-Shik Lee¹

Affiliations

¹ College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
² Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
³ Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis Regulatory Proteins / metabolism*
Bacillus subtilis / chemistry*
Calcium-Binding Proteins / metabolism*
Caspase 1 / metabolism
Cytokines / metabolism*
DNA-Binding Proteins / metabolism*
Glutamic Acid / pharmacology
Glycine max
Inflammasomes / metabolism*
Inflammation / pathology
Inflammation Mediators / metabolism
Macrophages / drug effects
Macrophages / metabolism
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Polyglutamic Acid / analogs & derivatives*
Polyglutamic Acid / chemistry
Polyglutamic Acid / pharmacology
Signal Transduction / drug effects
Toll-Like Receptor 4 / metabolism
Up-Regulation / drug effects*

Substances

Aim2 protein, mouse
Apoptosis Regulatory Proteins
Calcium-Binding Proteins
Cytokines
DNA-Binding Proteins
Inflammasomes
Inflammation Mediators
Ipaf protein, mouse
NLR Family, Pyrin Domain-Containing 3 Protein
Toll-Like Receptor 4
poly(gamma-glutamic acid)
Polyglutamic Acid
Glutamic Acid
Caspase 1