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

Ahn, Huijeong; Jeon, Eunsaem; Kim, Jin‐Chul; Kang, Seung Goo; Yoon, Sung‐il; Ko, Hyun‐Jeong; Kim, Pyeung-Hyeun; Lee, Geun‐Shik

doi:10.1038/s41598-017-01462-4

Cited by 58 publications

(34 citation statements)

References 45 publications

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“…The effects of lentinan on inflammation have been previously studied. Ahn found that lentinan attenuates AIM2 and non‐canonical inflammation while increasing pro‐inflammatory cytokines via TLR . In the current study, we found that lentinan down‐regulated LPS‐induced TLR4‐mediated NF‐κB signalling pathway and the expression of various inflammatory cytokines, which are key factors in leucocyte extravasation, colitis and CAC .…”

Section: Discussionsupporting

confidence: 59%

“…Ahn found that lentinan attenuates AIM2 and non-canonical inflammation while increasing pro-inflammatory cytokines via TLR. 51 In the current study, we found that lentinan down-regulated LPSinduced TLR4-mediated NF-κB signalling pathway and the expression of various inflammatory cytokines, which are key factors in leucocyte extravasation, colitis and CAC. 52 For example, it reduced the expression of IL-13 and CD30L, which are two key factors in IBD and CAC.…”

Section: Discussionmentioning

confidence: 49%

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Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

Liu

Zhao

et al. 2018

J Cellular Molecular Medi

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In this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis‐associated cancer (CAC). Lentinan decreased the disease activity index and macroscopic and microscopic colon tissue damage in dextran sulphate sodium (DSS)‐induced or TNBS‐induced models of colitis. High‐dose lentinan was more effective than salicylazosulfapyridine in the mouse models of colitis. Lentinan decreased the number of tumours, inflammatory cell infiltration, atypical hyperplasia and nuclear atypia in azoxymethane/DSS‐induced CAC model. It also decreased the expression of pro‐inflammatory cytokines, such as IL‐13 and CD30L, in IBD and CAC model mice possibly by inhibiting Toll‐like receptor 4 (TLR4)/NF‐κB signalling and the expression of colon cancer markers, such as carcinoembryonic antigen, cytokeratin 8, CK18 and p53, in CAC model mice. In addition, lentinan restored the intestinal bacterial microbiotal community structure in IBD model mice. Thus, it shows therapeutic potential in IBD and CAC model mice possibly by inhibiting TLR4/NF‐κB signalling‐mediated inflammatory responses and disruption of the intestinal microbiotal structure.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 49%

Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

Liu

Zhao

et al. 2018

J Cellular Molecular Medi

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“…Here, we found that ELNs from shiitake mushrooms strongly inhibited NLRP3 inflammasome activity but not AIM2 inflammasome activity (Figure 2). This function apparently is not mediated by the well-characterized biomolecule lentinan in shiitake mushrooms because lentinan was shown to specifically inhibit activation of the AIM2 inflammasome, but not the NLRP3 inflammasome [52]. Therefore, our research indicated that the newly identified component ELNs in shiitake mushrooms contribute to their anti-inflammatory functions.…”

Section: Discussionmentioning

confidence: 77%

Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

Liu

Chen

et al. 2020

Nutrients

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Fulminant hepatic failure (FHF) is a rare, life-threatening liver disease with a poor prognosis. Administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) triggers acute liver injury in mice, simulating many clinical features of FHF in humans; therefore, this disease model is often used to investigate potential therapeutic interventions to treat FHF. Recently, suppression of the nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome, was shown to alleviate the severity of GalN/LPS-induced liver damage in mice. Therefore, the goal of this study was to find dietary exosome-like nanoparticles (ELNs) with therapeutic potential in curbing FHF by suppressing the NLRP3 inflammasome. Seven commonly consumed mushrooms were used to extract ELNs. These mushrooms were found to contain ELNs composed of RNAs, proteins, and lipids. Among these mushroom-derived ELNs, only shiitake mushroom-derived ELNs (S-ELNs) substantially inhibited NLRP3 inflammasome activation by preventing inflammasome formation in primary macrophages. S-ELNs also suppressed the secretion of interleukin (IL)-6, as well as both protein and mRNA levels of the Il1b gene. Remarkably, pre-treatment with S-ELNs protected mice from GalN/LPS-induced acute liver injury. Therefore, S-ELNs, identified as potent new inhibitors of the NLRP3 inflammasome, represent a promising class of agents with the potential to combat FHF.

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“…The β-glucan structure of lentinan can directly bind to dectin-14 that is expressed on the surface of neutrophils, macrophages, and natural killer cells [16]. As a polysaccharide, lentinan also has various effects on inflammatory signalling pathways, such as NF-kB, MAPK, and the inflammasome [17]. Although lentinan promotes the activity of macrophages and CTLs, it may also inhibit the progress of inflammation in vivo by blocking proinflammatory cytokines, such as IL-1β and IL-18 [17].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to activating the NF-kB and MAPK signalling pathways, lentinan alters inflammasome activation and cytokine maturation [13]. It triggers expression of proinflammatory cytokines via the NLRP3 inflammasome and selectively inhibits cytokine secretion in response to AIM2 inflammasome activation in a colitis model [17]. These findings may explain why lentinan alone decreased cytokine production on further LPS stimulation.…”

Section: Discussionmentioning

confidence: 99%

Lentinan relieves hepatitis B surface antigen induced functional impairment of monocytes/macrophages

Fang¹,

Li²,

Huang³

et al. 2018

Trop. J. Pharm Res

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Purpose: To investigate the efficacy of lentinan in relieving hepatitis B surface antigen (HBsAg)induced functional impairment of monocytes/macrophages. Methods: Monocytic cell line THP-1 was incubated with lentinan and HBsAg for 24 h and then stimulated with LPS (Lipopolysaccharide). The expression levels of interleukin-1β (IL-1β), IL-12 and tumour necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent (ELISA) assays and quantitative reverse transcriptase-PCR (q-PCR). Protein levels of IkB-α, phospho-ERK, and phospho-p38 were measured by western blotting. Results: THP-1 cells treated with lentinan and HBsAg showed higher IL-1β, IL-12, and TNF-α levels than cells treated with HBsAg alone. The underlying mechanisms were associated with NF-kB and MAPK signal pathways. Decreased expression of IkB-α and phospho-ERK and increased expression of phospho-JNK and phospho-p38 were observed in cells treated with lentinan and HBsAg when compared with cells treated with HBsAg alone (p < 0.001). THP-1 cells incubated with 500 μg/mL lentinan secreted lower levels of cytokines than did control cells after LPS stimulation, suggesting an anti-inflammatory effect for lentinan. Conclusion: Lentinan shows both pro-and anti-inflammatory functions and may be a promising candidate for hepatitis B virus (HBV) treatment.

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

Cited by 58 publications

References 45 publications

Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice

Lentinan relieves hepatitis B surface antigen induced functional impairment of monocytes/macrophages

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