Critical role of toll-like receptor 4 (TLR4) in ricin toxin-induced inflammatory responses in macrophages

Dong, Mingxin; Yu, Haotian; Wang, Yan; Sun, Chengbiao; Chang, Ying; Yin, Qiliang; Zhao, Guiru; Xu, Na; Liu, Wensen

doi:10.1016/j.toxlet.2019.12.021

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…In previous studies, we have verified the interaction between RT and TLR4 through immunoprecipitation (Dong et al, 2019), which supports the molecular docking model of RT and TLR4 in this section.…”

Section: Computer Simulation Of the Interface Of Rt And Tlr4supporting

confidence: 87%

“…TLR4 signaling pathways are known to play important roles in immune cell activation (Kawai and Akira, 2010;Gay et al, 2014). In previous studies, we have verified the interaction between RT and TLR4 through immunoprecipitation (Dong et al, 2019). In this study, when RAW264.7 cells were treated with RTB, it was observed that recombinant RTB stimulated expression of the TLR4 protein.…”

Section: Discussionsupporting

confidence: 58%

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Recombinant Ricin Toxin Binding Subunit B (RTB) Stimulates Production of TNF-α by Mouse Macrophages Through Activation of TLR4 Signaling Pathway

et al. 2020

Front. Pharmacol.

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Ricin toxin binding subunit B (RTB) is a galactose-binding lectin protein derived from the beans of the castor oil plant (Ricinus communis). Our previous studies have reported a direct immunomodulatory effect of recombinant RTB, which stimulates RAW264.7 cells to produce cytokines including TNF-a. However, the role of RTB in innate immune response and its specific mechanism have not been reported in detail. In this work, the results showed that RTB treatment of macrophages significantly increased TLR4 protein levels. RTB also activated TLR4 downstream events, including MyD88, IRAK, and TRAF6, resulting in macrophage activation and TNF-a production. This process is reflected in the increase of IkB phosphorylation. TLR4 knockdown macrophages treated with RTB exhibited greatly reduced IkB phosphorylation and TNF-a secretion. Moreover, treatment with MyD88 inhibitor also suppressed TNF-a production. The docking of RT and TLR4 was simulated by computer, and the contact residues were concentrated on RTB. Our results suggest that recombinant RTB can activate mouse macrophages to secrete TNF-a through activation of NF-kB via the TLR4 signaling pathways.

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Section: Computer Simulation Of the Interface Of Rt And Tlr4supporting

confidence: 87%

Section: Discussionsupporting

confidence: 58%

Recombinant Ricin Toxin Binding Subunit B (RTB) Stimulates Production of TNF-α by Mouse Macrophages Through Activation of TLR4 Signaling Pathway

et al. 2020

Front. Pharmacol.

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“…The expression levels of TLR4, NF-κB P65, iNOS, and inflammatory factors in cells were found to have significantly increased after the addition of LPS. Such results could be attributed to LPS directly activating and promoting TLR4 expression, thereby activating the NF-κB site (Dong et al, 2020). When NF-κB is activated, IκBα will be phosphorylated and degraded, and result in phosphorylation of NF-κB heterodimers (p50/p65), which in turn leads to enhanced nuclear translocation activity (Xin et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice

Liu

Zhou

et al. 2021

J Food Biochem

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In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNFα, IL-1β, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential antiinflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. Practical applicationsIn recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity.

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“…In the liver, Kupffer cells are similarly sensitive to ricin-induced killing in vitro and ex vivo following toxin delivery by injection (22)(23)(24). The sensitivity of macrophages is borne out in vitro, as ricin has been shown to trigger apoptosis in numerous macrophage and monocytic cell lines of mouse and human origin (21,(25)(26)(27)(28)(29). The sensitivity of macrophages to ricin is due in part to the mannose receptor (MR), which recognizes the mannose side chains or RTA and RTB and facilitates toxin uptake by a mechanism that remains poorly understood (23,30).…”

Section: Accepted Articlementioning

confidence: 99%

Differential ER stress as a driver of cell fate following ricin toxin exposure

Peterson-Reynolds

Mantis

2021

FASEB BioAdvances

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Acute respiratory distress syndrome (ARDS) is a lifethreatening complication brought about by a variety of insults ranging from physical injury to viral infection to toxin exposure. One such provocateur is ricin, a type II ribosome-inactivating protein (RIP) or ribotoxin found in castor beans (Ricinus communis). 1-3 Ricin's B subunit (RTB) is a Gal/GalNAc-specific lectin that adheres to glycoproteins and glycolipids on cell surfaces and promotes

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Critical role of toll-like receptor 4 (TLR4) in ricin toxin-induced inflammatory responses in macrophages

Cited by 17 publications

References 41 publications

Recombinant Ricin Toxin Binding Subunit B (RTB) Stimulates Production of TNF-α by Mouse Macrophages Through Activation of TLR4 Signaling Pathway

Recombinant Ricin Toxin Binding Subunit B (RTB) Stimulates Production of TNF-α by Mouse Macrophages Through Activation of TLR4 Signaling Pathway

Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice

Differential ER stress as a driver of cell fate following ricin toxin exposure

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