Dataset Information

Annatto Tocotrienol Attenuates NLRP3 Inflammasome Activation in Macrophages.

ABSTRACT: Accumulating evidence suggests that aberrant innate immunity is closely linked to metabolic diseases, including type 2 diabetes. In particular, activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and subsequent secretion of interleukin 1? (IL-1?) are critical determinants that precipitate disease progression. The seeds of annatto (Bixa orellana L.) contain tocotrienols (T3s), mostly (>90%) in the ? form (?T3). The aim of this study was to determine whether annatto T3 is effective in attenuating NLRP3 inflammasome activation in macrophages. Our results showed that annatto ?T3 significantly attenuated NLRP3 inflammasome by decreasing IL-1? reporter activity, IL-1? secretion, and caspase-1 cleavage against lipopolysaccharide (LPS) followed by nigericin stimulation. With regard to mechanism, annatto ?T3 1) reduced LPS-mediated priming of the inflammasome and 2) dampened reactive oxygen species production, the second signal required for assembly of the NLRP3 inflammasome in macrophages. Our work suggests that annatto ?T3 may hold therapeutic potential for delaying the onset of NLRP3 inflammasome-associated chronic metabolic diseases.

SUBMITTER: Buckner T

PROVIDER: S-EPMC5998354 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Annatto Tocotrienol Attenuates NLRP3 Inflammasome Activation in Macrophages.

Buckner Teresa T Fan Rong R Kim Yongeun Y Kim Jiyoung J Chung Soonkyu S

Current developments in nutrition 20170531 6

Accumulating evidence suggests that aberrant innate immunity is closely linked to metabolic diseases, including type 2 diabetes. In particular, activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and subsequent secretion of interleukin 1β (IL-1β) are critical determinants that precipitate disease progression. The seeds of annatto (<i>Bixa orellana L</i>.) contain tocotrienols (T3s), mostly (>90%) in the δ form (δT3). The aim of this study was to determine wh ...[more]

PMID: 29955706

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Project description:Human parvovirus B19 (B19V) has been strongly associated with a variety of inflammatory disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease and systemic lupus erythematosus. Non‑structural protein 1 (NS1) of B19V has been demonstrated to play essential roles in the pathological processes of B19V infection due to its regulatory properties on inflammatory cytokines. Celastrol, a quinone methide isolated from Tripterygium wilfordii, has displayed substantial potential in treating inflammatory diseases, such as psoriasis and RA. However, little is known about the effects of celastrol on B19V NS1‑induced inflammation. Therefore, cell viability assay, migration assay, phagocytosis analysis, zymography assay, ELISA and immunoblotting were conducted to verify the influences of celastrol on macrophages. The present study reported the attenuating effects of celastrol on B19V NS1‑induced inflammatory responses in macrophages derived from human acute monocytic leukemia cell lines, U937 and THP‑1. Although the migration was not significantly decreased by celastrol in both U937 and THP‑1 macrophages, significantly decreased viability, migration and phagocytosis were detected in both B19V NS1‑activated U937 and THP‑1 macrophages in the presence of celastrol. Additionally, celastrol significantly decreased MMP‑9 activity and the levels of inflammatory cytokines, including IL‑6, TNF‑α and IL‑1β, in B19V NS1‑activated U937 and THP‑1 cells. Notably, significantly decreased levels of NLR family pyrin domain‑containing 3, apoptosis‑associated speck‑like, caspase‑1 and IL‑18 proteins were observed in both B19V NS1‑activated U937 and THP‑1 cells in the presence of celastrol, indicating the involvement of the inflammasome pathway. To the best of our knowledge, the present study is the first to report on the attenuating effects of celastrol on B19V NS1‑induced inflammatory responses in macrophages, suggesting a therapeutic role for celastrol in B19V NS1‑related inflammatory diseases.

Dataset Information

Annatto Tocotrienol Attenuates NLRP3 Inflammasome Activation in Macrophages.

Publications

Annatto Tocotrienol Attenuates NLRP3 Inflammasome Activation in Macrophages.

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