Lentinan from shiitake selectively attenuates AIM2 and non-canonical inflammasome activation while inducing pro-inflammatory cytokine production

• Published in: Scientific reports Vol. 7; no. 1; pp. 1314 - 12
• Main Authors: Ahn, Huijeong, Jeon, Eunsaem, Kim, Jin-Chul, Kang, Seung Goo, Yoon, Sung-il, Ko, Hyun-Jeong, Kim, Pyeung-Hyeun, Lee, Geun-Shik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-05-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 631/250/127/1213; 631/250/256/2177; 64/60; 82; 82/80; 96; Bone marrow; Caspase; Caspase-1; Cell activation; Cytokines; Endotoxins; Humanities and Social Sciences; Immune system; Inflammasomes; Inflammation; Interleukin 18; Intravenous administration; Lentinan; Lethality; Lipopolysaccharides; Listeria; Listeria monocytogenes; Macrophages; Melanoma; multidisciplinary; Myeloid cells; Rodents; Science; Science (multidisciplinary); TLR4 protein; Toll-like receptors; β-Glucan
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-01462-4

Lentinan extracted from shiitake (
Lentinula edodes
) is a β-glucan that has been reported as an intravenous anti-tumor polysaccharide via enhancement of the host immune system. In this study, we determined the effect of lentinan on inflammasome activation, a multi-protein platform, in myeloid cells. Mouse bone marrow-derived macrophages were treated with lentinan with/without inflammasome triggers, and maturation of interleukin (IL)-1β, IL-18, or caspase-1 was measured as a readout of inflammasome activation. As a result, lentinan selectively inhibited absent in melanoma 2 (AIM2) inflammasome activation. In addition, lentinan up-regulated pro-inflammatory cytokines and induced expression of inflammasome-related genes through toll-like receptor 4 signaling. Furthermore, we assessed the effect of lentinan on mice treated with
Listeria monocytogenes
or lipopolysaccharide as an AIM2 or non-canonical inflammasome-mediated model. Lentinan attenuated IL-1β secretion resulting from
Listeria-
mediated AIM2 inflammasome activation and reduced endotoxin lethality via inhibition of non-canonical inflammasome activation. Thus, lentinan is suggested as an anti-AIM2 and anti-non-canonical inflammasome candidate despite its up-regulation of cytokine expression.