Inhibition of intimal hyperplasia in murine aortic allografts by administration of a small-molecule TLR4 inhibitor TAK-242

Wu, Chuangyan; Ding, Xiangchao; Zhou, Cheng; Sun, Yuan; Wu, Jie; Zhang, Anchen; Huang, Xintang; Ren, Lingyun; Wang, Ke; Deng, Peng; Zhang, Yue; Chen, Jiuling; Wang, Sihua; Xia, Jiahong

doi:10.1038/s41598-017-16160-4

Cited by 11 publications

(11 citation statements)

References 38 publications

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“…Previous studies by others also showed that the inhibition of TLR-4 led to the inhibition of LPS [20] and megalo-type α-1,6-glucosaccharideinduced NO production [21]. TLR-4 inhibition also decreased immunoexpression of iNOS in the microglia of day old Wistar rats [22] and allografts [23]. It is of note that in this study iNOS expression was significant even in the un-stimulated group, which was contrary to our expectations.…”

Section: Discussioncontrasting

confidence: 99%

The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

Abbas

Suppian

2019

J Infect Dev Ctries

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Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). Methodology: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. Results: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. Conclusions: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

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Section: Discussioncontrasting

confidence: 99%

The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

Abbas

Suppian

2019

J Infect Dev Ctries

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“…Thus, TAK-242 may be a promising drug for the treatment of inflammatory diseases involving TLR4, such as sepsis [ 21 ]. In addition to being able to relieve acute kidney injury, TAK-242 can ameliorate inflammatory injury in cerebral hemorrhage and acute cerebral ischemia/reperfusion, and can also inhibit intimal hyperplasia in murine aortic allografts [ 22 – 25 ]. In addition, TLR4 promotes the production of inflammatory cytokines through MyD88- and TRIF-dependent pathways [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway

et al. 2020

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Background: The goal of the present study was to investigate the effects of TAK-242 on the gut microbiota and the TLR4/JAK2/STAT3 signaling pathway in mice with dextran sulfate sodium (DSS)-induced colitis. Results: At the phylum level, Bacteroidetes, Firmicutes, Actinobacteria, Cyanobacteria, Epsilonbacteraeota and Proteobacteria were the primary microbiota in the five groups. TAK-242 treatment significantly enhanced Verrucomicrobia and Actinobacteria; significantly decreased Cyanobacteria, Epsilonbacteraeota and Proteobacteria; and particularly promoted the growth of Akkermansia. TAK-242 markedly alleviated DSS-induced colitis symptoms and colonic lesions by promoting IL-10 release, inhibiting IL-17 release, downregulating TLR4 and JAK2/STAT3 mRNA and protein expression and increasing JAK2/STAT3 phosphorylation. Conclusion: TAK-242 modulates the structure of the gut microbiota in colitis and may be a novel therapeutic candidate for ulcerative colitis.

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“…HMGB1 has two receptors, i.e., TLR4 and RAGE ( 20 ). The question of which receptor(s) play a critical role in HNC-BP remains unanswered.…”

Section: Discussionmentioning

confidence: 99%

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer

et al. 2020

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Advanced head and neck cancer (HNC) can invade facial bone and cause bone pain, thus posing a significant challenge to the quality of life of patients presenting with advanced HNC. The present study was designed to investigate HNC bone pain (HNC-BP) in an intratibial mouse xenograft model that utilized an HNC cell line (SAS cells). These mice develop HNC-BP that is associated with an expression of phosphorylated ERK1/2 (pERK1/2), which is a molecular indicator of neuron excitation in dorsal root ganglia (DRG) sensory neurons. Our experiments demonstrated that the inhibition of high mobility group box 1 (HMGB1) by short hairpin (shRNA) transduction, HMGB1 neutralizing antibody, and HMGB1 receptor antagonist suppressed the HNC-BP and the pERK1/2 expression in DRG. It was also observed that HNC-derived HMGB1 increased the expression of the acid-sensing nociceptor, transient receptor potential vanilloid 1 (TRPV1), which is a major cause of osteoclastic HNC-BP in DRG. Collectively, our results demonstrated that HMGB1 originating in HNC evokes HNC-BP via direct HMGB1 signaling and hypersensitization for the acid environment in sensory neurons.

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Inhibition of intimal hyperplasia in murine aortic allografts by administration of a small-molecule TLR4 inhibitor TAK-242

Cited by 11 publications

References 38 publications

The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway

High mobility group box 1 induces bone pain associated with bone invasion in a mouse model of advanced head and neck cancer

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