Spirulina maxima extract prevents activation of the NLRP3 inflammasome by inhibiting ERK signaling

Abstract

Spirulina maxima extract prevents activation of the NLRP3 inflammasome by inhibiting ERK signaling Sungwoo chei, Hyun-Ji oh, Ji-Hyeon Song, Young-Jin Seo, Kippeum Lee, Kui-Jin Kim & Boo-Yong Lee * The blue-green alga Spirulina maxima is a microscopic filamentous cyanobacterium. Spirulina was recently reported to elicit beneficial effects such as reducing cholesterol and inducing weight loss; however, its effects on inflammation are unknown. To determine the effect of S. maxima extract (SMe) on innate immunity, we investigated the NLRP3 inflammasome activation, which is a multiprotein scaffolding complex that plays important roles in innate immune responses to many pathogenic infections in macrophages. SME suppressed lipopolysaccharide (LPS)-induced upregulation of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-12, IL-1β, and IL-18 in RAW264.7 cells. In addition, SME attenuated LPS-induced NLRP3 inflammasome activation, and thus pro-IL-1β could not be cleaved to IL-1β by activated caspase-1, which is activated by the NLRP3 inflammasome in RAW264.7 cells. Moreover, SME inhibited LPS-induced phosphorylation of extracellular signalregulated kinase (ERK) in RAW264.7 cells, and attenuated the generation of ERK1 induced-reactive oxygen species (ROS), resulting in decreased expression of NF-κB. These findings suggest that SME suppresses the effects of the NLRP3 inflammasome via regulation of extracellular signal-regulated kinase (ERK). In summary, we demonstrated that SME prevents activation of the NLRP3 inflammasome by inhibiting ERK signaling. Inflammation plays an important role in the innate immune response to pathogen infection 1. Insufficient or excessive inflammation can lead to various chronic disorders related to the innate immune system. There are distinct innate immune responses to detection of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns 2. PAMPs activate innate immune responses that protect the host against infection. Bacterial lipopolysaccharides (LPS) are considered to be the prototypical class of PAMP 3. LPS is a component of the outer cell membrane of Gram-negative bacteria and may activate macrophages 4,5. Inflammasome activation is a crucial signaling node mediated by the innate immune system. Inflammasomes are categorized according to their sensor protein: NLRP3 (NOD-like receptor family, pyrin domain-containing 3), AIM2 (absent in melanoma-2), NLRC4 (NOD-like receptor family CARD domain-containing protein 4), and NLRP1 (NOD-like receptor family, pyrin domain-containing 1) 6-8. The NLRP3 inflammasome is a widely studied multiprotein scaffolding complex 9-11. LPS stimulation induces activation of the NLRP3 inflammasome 12-14 , which catalyzes the proteolytic maturation of pro-caspase-1 to activated caspase-1 10,15,16. Unlike other inflammatory cytokines, IL-1β is synthesized in as inactive immature form (pro-IL-1β that must undergo cleavage by caspase-1 to obtain the activated form (IL-1β) 17. Macrophages stimulated with LPS activate ...

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