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

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Cellular & Molecular Immunology 2018年第2期15卷 111-119页

作者： huijeong ahn Seung Goo Kang Sung-il Yoon Pyeung-Hyeun Kim Doo Kim Geun-Shik Lee College of Veterinary Medicine and Institute of Veterinary Science Kangwon National UniversityChuncheon24341GangwonRepublic of Korea Department of Systems Immunology College of Biomedical ScienceKangwon National UniversityChuncheon24341GangwonRepublic of Korea Department of Molecular Bioscience School of Biomedical ScienceKangwon National UniversityChuncheon24341GangwonRepublic of Korea

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 ***,the effect ofγ-PGA on inflammasome activation has not yet been studied in ***,which are intracellular multi-protein complexes,promote acute and chronic inflammation via interleukin-1βor interleukin-18 maturation,and they are known targets for metabolic syndromes and *** this study,we observed thatγ-PGA attenuated NLRP3,NLRC4 and AIM2 inflammasome activation,whereas it upregulated pro-inflammatory cytokine expression in human and murine ***γ-PGA had conflicting effects on cytokine production and maturation,it clearly alleviated the severity of lipopolysaccharide-induced endotoxin shock in an animal ***,we suggestγ-PGA as a candidate to control inflammasome-mediated disorders.

关键词： Cheonggukjang cytokines inflammasome macrophages poly-gamma-glutamate

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Role of inflammasome regulation on immune modulators

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The Journal of Biomedical Research 2018年第6期32卷 401-410页

作者： huijeong ahn Hyuk Moo Kwon Eunsong Lee Pyeung-Hyeun Kim Eui-Bae Jeung Geun-Shik Lee College of Veterinary Medicine and Institute of Veterinary Science Department of Molecular Bioscience School of Biomedical ScienceKangwon National UniversityChuncheon 24341Republic of Korea Laboratory of Veterinary Biochemistry and Molecular Biology College of Veterinary MedicineChungbuk National UniversityCheongju 28644Republic of Korea.

Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing *** cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.

关键词： immune modulator inflammasome macrophages interleukin-1β

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