TY - JOUR
T1 - Exosome-like Nanoparticles from Ginger Rhizomes Inhibited NLRP3 Inflammasome Activation
AU - Chen, Xingyi
AU - Zhou, You
AU - Yu, Jiujiu
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) 1P20GM104320 Nebraska Center for the Prevention of Obesity Diseases through Dietary Molecules (NPOD) Seed Grant and Project Leader Grant, and the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) Hatch Project 1015948. The authors acknowledge the use of the Biomedical and Obesity Research Core (BORC) of the NPOD and the Systems Biology (Microscopy) Core of the Nebraska Center for Integrated Biomolecular Communication (NCIBC) at the University of Nebraska Lincoln. We thank the assistance of Dr. Steven Kachman (NPOD) for statistical analysis and Terri Fangman (NCIBC) for confocal operation. We also thank Dr. Janos Zempleni and his laboratory members for the technical assistance and invaluable discussions and Dr. Soonkyu Chung for critical review of the manuscript.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - The nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immune responses, and its aberrant activation is implicated in the pathogenesis of many diseases such as Alzheimer's disease and type 2 diabetes. Targeting the NLRP3 inflammasome could hold promise to combat these complex diseases, but therapies specifically inhibiting the NLRP3 inflammasome have not been developed for patient treatment. The current study aimed to identify food-borne exosome-like nanoparticles (ELNs) that inhibit NLRP3 inflammasome activity. Nine vegetables or fruits were selected to extract ELNs, which were examined for their inhibitory effects on activation of the NLRP3 inflammasome in primary macrophages. Although most of the tested ELNs posed minimal impacts, the ELNs from ginger rhizomes (G-ELNs) strongly inhibited NLRP3 inflammasome activation. The G-ELNs contained lipids, proteins, and RNAs and were easily taken up by macrophages. G-ELN treatment suppressed pathways downstream of inflammasome activation including caspase1 autocleavage, interleukin (IL)-1β and IL-18 secretion, and pyroptotic cell death. Apoptotic speck protein containing a caspase recruitment domain (ASC) oligomerization and speck formation assays indicated that G-ELNs blocked assembly of the NLRP3 inflammasome. The lipids in G-ELNs, rather than the RNAs or proteins, were responsible for the inhibitory activity observed. Together, the data suggested G-ELNs as new potent agents that block NLRP3 inflammasome assembly and activation. The unique features of G-ELNs including biomolecule protection and tissue bioavailability should facilitate the development of G-ELN-based therapy to target the NLRP3 inflammasome in the disease settings.
AB - The nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immune responses, and its aberrant activation is implicated in the pathogenesis of many diseases such as Alzheimer's disease and type 2 diabetes. Targeting the NLRP3 inflammasome could hold promise to combat these complex diseases, but therapies specifically inhibiting the NLRP3 inflammasome have not been developed for patient treatment. The current study aimed to identify food-borne exosome-like nanoparticles (ELNs) that inhibit NLRP3 inflammasome activity. Nine vegetables or fruits were selected to extract ELNs, which were examined for their inhibitory effects on activation of the NLRP3 inflammasome in primary macrophages. Although most of the tested ELNs posed minimal impacts, the ELNs from ginger rhizomes (G-ELNs) strongly inhibited NLRP3 inflammasome activation. The G-ELNs contained lipids, proteins, and RNAs and were easily taken up by macrophages. G-ELN treatment suppressed pathways downstream of inflammasome activation including caspase1 autocleavage, interleukin (IL)-1β and IL-18 secretion, and pyroptotic cell death. Apoptotic speck protein containing a caspase recruitment domain (ASC) oligomerization and speck formation assays indicated that G-ELNs blocked assembly of the NLRP3 inflammasome. The lipids in G-ELNs, rather than the RNAs or proteins, were responsible for the inhibitory activity observed. Together, the data suggested G-ELNs as new potent agents that block NLRP3 inflammasome assembly and activation. The unique features of G-ELNs including biomolecule protection and tissue bioavailability should facilitate the development of G-ELN-based therapy to target the NLRP3 inflammasome in the disease settings.
KW - NLRP3 inflammasome
KW - exosomes
KW - ginger
KW - inflammation
KW - nanoparticles
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U2 - 10.1021/acs.molpharmaceut.9b00246
DO - 10.1021/acs.molpharmaceut.9b00246
M3 - Article
C2 - 31038962
AN - SCOPUS:85066798612
VL - 16
SP - 2690
EP - 2699
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 6
ER -