Abstract
The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to the pathogenesis of a wide variety of human diseases. Although many drugs and inhibitors have been developed to treat NLRP3-associated diseases, only limited clinical data support their efficacy and safety. Chlorella, a unicellular green alga that is widely and safely used as a food supplement, contains various antioxidants. In this study, we obtained a fat-soluble extract from Chlorella (CE) and demonstrated that it reduced NLRP3 inflammasome activation by inhibiting mitochondrial reactive oxygen species and caspase-1 activation. In addition, CE supplementation attenuated lipopolysaccharide-induced interleukin 1β transcription through activation of hypoxia-inducible factor 1α in vitro and in vivo. As Chlorella is a safe and useful food supplement, it may be a practical pharmacological approach for treating NLRP3-driven diseases.
Highlights
The NOD-like receptor (NLR) family protein NOD, LRR, and pyrin domain-containing protein 3 (NLRP3) is an intracellular sensor molecule that detects many pathogen and host-derived factors [1, 2]
When we compared the kinetics of cytokine gene expression induced by LPS, the expression of Il-1b and Il-6 was significantly downregulated in response to LPS in RAW264 macrophages (p < 0.05; Figure 1B) and peritoneal macrophages (pMACs) (p < 0.05; Figure 1C) with CE
It is not clear whether CE has an inhibitory effect on LPS-induced gene expression of Tnfa and Ifnb1 in mouse macrophages (Figures 1B,C), we thought that CE suppresses LPS-induced Il-1b transcription
Summary
The NOD-like receptor (NLR) family protein NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) is an intracellular sensor molecule that detects many pathogen and host-derived factors [1, 2]. Drugs or supplements that safely inhibit the NLRP3 inflammasome are needed. Activation of the NLRP3 inflammasome depends on two functionally distinct steps: priming and activation [2]. The priming step (signal 1) begins with the recognition by pattern recognition receptors (PRRs) of extracellular molecules such as lipopolysaccharide (LPS: TLR4 agonist). LPS stimulation increases nuclear factor-κB (NF-κB)-mediated NLRP3 and pro-interleukin (IL)1β expression. Enhanced glycolysis and hypoxia inducible factor (HIF)-1α activation by LPS stimulation supports increased Il-1b transcription [6, 7]. NLRP3 recruits and binds to apoptosis-associated speck-like protein containing a CARD (ASC). NLRP3 and ASC interact with the cysteine protease caspase-1 to form a super-complex termed the inflammasome
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
