Fucoxanthin from microalgae Phaeodactylum tricornutum inhibits pro-inflammatory cytokines by regulating both NF-\u03baB and NLRP3 inflammasome activation

A-Hyeon Lee,Jong-Hwi Park,Seung-Hoon Yang,Song Yi Koo,Hye-Yoon Shin,Sang Min Kim

doi:10.1038/s41598-020-80748-6

Abstract

Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are mediated by the activation of various kinds of signaling pathways in the innate immune system. Particularly, NF-κB and NLRP3 inflammasome signaling are involved in the production and secretion of these cytokines. Each signaling is participated in the two steps necessary for IL-1β, a representative pro-inflammatory cytokine, to be processed into a form secreted by cells. In the priming step stimulated by LPS, pro-IL-1β is synthesized through NF-κB activation. Pro-IL-1β cleavages into mature IL-1β by formed NLRP3 inflammasome in the activation step induced by ATP. The mature form of IL-1β is subsequently secreted out of the cell, causing inflammation. Moreover, IL-6 and TNF-α are known to increase in NLRP3 inflammasome-mediated conditions. Here, we found that fucoxanthin, one of the major components of Phaeodactylum tricornutum, has an inhibitory effect on NF-κB and NLRP3 inflammasome activation induced by the combination of LPS and ATP in bone marrow-derived immune cells as well as astrocytes. Fucoxanthin, which is abundant in the EtOH fraction of Phaeodactylum tricornutum extracts, has shown to have less cell toxicity and found to decrease the production of major pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Fucoxanthin has also shown to suppress the expression of cleaved caspase-1 and the oligomerization of ASC, which are the main components of the NLRP3 inflammasome. Furthermore, phosphorylated IκBα and pro-IL-1β expression decreased in the presence of fucoxanthin, suggesting that fucoxanthin can negatively regulate the priming step of inflammasome signaling. Thus, our results provide reliable evidence that fucoxanthin may serve as a key candidate in the development of potential therapeutic agents for inflammatory diseases as well as neurodegenerative diseases caused by NF-κB and NLRP3 inflammasome activation.

Highlights

Inflammation is a mechanism of the body to protect against adverse substances, such as invading pathogens, damaged cells, or environmental irritants[1]
To evaluate the biological and physiological effects of Phaeodactylum tricornutum extracts on immune cells, we pre-treated each extract to bone marrowderived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs) for 4 h before LPS and ATP stimulation to induce inflammation
We found that pre-treatment with each extract reduced IL-1β production in both BMDMs (Fig. 2I) and BMDCs (Fig. 2J)

Summary

Introduction

Inflammation is a mechanism of the body to protect against adverse substances, such as invading pathogens, damaged cells, or environmental irritants[1]. This type of prolonged inflammation can contribute to the development of diseases such as: rheumatoid arthritis, type 2 diabetes, and neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease)[4,5]. IL-1β is first synthesized as a pro-form by stimulation of pathogen-associated molecular patterns (PAMPs) such as LPS on specific pattern-recognition receptors (PRRs) of immune cells through the activation of NF-κB signaling (priming step). Pro-form IL-1β is matured through the NLRP3 inflammasome activation, stimulated by damaged-associated molecular patterns (DAMPs) such as ATP or uric acid (activating step)[6,7]. TNF-α has a function on the activation of NLRP3 inflammasome components in inflammatory diseases. IL-6 and TNF-α are important mediators for NLRP3 inflammasome a ctivation[11]

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