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

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-α. H...

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Main Authors: Na Xu (Author), Kaikai Yu (Author), Haotian Yu (Author), Jianxu Zhang (Author), Yang Yang (Author), Mingxin Dong (Author), Yan Wang (Author), Ying Chang (Author), Yucheng Sun (Author), Yanguang Hou (Author), Chengbiao Sun (Author), Jiayu Wan (Author), Wensen Liu (Author)
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Published: Frontiers Media S.A., 2020-09-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Na Xu  |e author 
700 1 0 |a Na Xu  |e author 
700 1 0 |a Kaikai Yu  |e author 
700 1 0 |a Haotian Yu  |e author 
700 1 0 |a Jianxu Zhang  |e author 
700 1 0 |a Yang Yang  |e author 
700 1 0 |a Mingxin Dong  |e author 
700 1 0 |a Yan Wang  |e author 
700 1 0 |a Ying Chang  |e author 
700 1 0 |a Ying Chang  |e author 
700 1 0 |a Yucheng Sun  |e author 
700 1 0 |a Yanguang Hou  |e author 
700 1 0 |a Chengbiao Sun  |e author 
700 1 0 |a Jiayu Wan  |e author 
700 1 0 |a Wensen Liu  |e author 
245 0 0 |a Recombinant Ricin Toxin Binding Subunit B (RTB) Stimulates Production of TNF-α by Mouse Macrophages Through Activation of TLR4 Signaling Pathway 
260 |b Frontiers Media S.A.,   |c 2020-09-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2020.526129 
520 |a 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-α. 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-α production. This process is reflected in the increase of IκB phosphorylation. TLR4 knockdown macrophages treated with RTB exhibited greatly reduced IκB phosphorylation and TNF-α secretion. Moreover, treatment with MyD88 inhibitor also suppressed TNF-α 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-α through activation of NF-κB via the TLR4 signaling pathways. 
546 |a EN 
690 |a ricin toxin binding subunit B 
690 |a macrophage 
690 |a TLR4 
690 |a cytokine 
690 |a signaling pathway 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 11 (2020) 
787 0 |n https://www.frontiersin.org/article/10.3389/fphar.2020.526129/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/6a4d394907ec42c6acaa0bff0ecccbe3  |z Connect to this object online.