NZ suppresses TLR4/NF-κB signalings and NLRP3 inflammasome activation in LPS-induced RAW264.7 macrophages

Xiang, Pengjun; Chen, Tong; Mou, Yi; Wu, Hui; Xie, Peng; Guo, Lu; Gong, Xiaoyi; Hu, Qinghua; Zhang, Yihua; Ji, Hui

doi:10.1007/s00011-015-0863-4

Cited by 102 publications

(58 citation statements)

References 35 publications

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“…As the receptor of LPS, TLR4 plays a principal role in the recognition of gram‐negative bacteria. MyD88 is an adaptor molecule in response to the interaction of TLR4 with LPS (Xiang et al, ). In the present study, our results showed that LPS treatment increased the protein levels of TLR4, MyD88, and NF‐κB in human MLs.…”

Section: Discussionmentioning

confidence: 99%

Isoforskolin and forskolin attenuate lipopolysaccharide‐induced inflammation through TLR4/MyD88/NF‐κB cascades in human mononuclear leukocytes

Shi

Wang³

et al. 2019

Phytotherapy Research

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The principal active component of isoforskolin (ISOF) is from the plant Coleus forskohlii , native to China, which has attracted much attention for its biological effects. We hypothesize that ISOF and forskolin (FSK) pretreatment attenuates inflammation induced by lipopolysaccharide (LPS) related to toll‐like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF‐κB) signaling. Mononuclear leukocytes (MLs) from healthy donors' blood samples were separated by using density gradient centrifugation. Protein levels of TLR4, MyD88, and NF‐κB were detected using western blot and inflammatory cytokines interleukin (IL) 1β, IL‐2, IL‐6, IL‐21, IL‐23, tumor necrosis factor (TNF) α, and TNF‐β were tested by enzyme‐linked immunosorbent assay and Quantibody array in MLs. Our results showed that LPS augmented the protein levels of TLR4, MyD88, and NF‐κB in MLs and the production of IL‐1β, IL‐2, IL‐6, IL‐21, IL‐23, TNF‐α, and TNF‐β in supernatants of MLs. Despite treatment with ISOF and FSK prior to LPS, the protein levels of TLR4, MyD88, NF‐κB, IL‐1β, IL‐2, IL‐6, IL‐21, IL‐23, TNF‐α, and TNF‐β in MLs were apparently decreased. roflumilast (RF) and dexamethasone (DM) had a similar effect on MLs with ISOF and FSK. Our results, for the first time, have shown that ISOF and FSK attenuate inflammation in MLs induced by LPS through down‐regulating protein levels of IL‐1β and TNF‐α, in which TLR4/MyD88/NF‐κB signal pathway could be involved.

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Section: Discussionmentioning

confidence: 99%

Isoforskolin and forskolin attenuate lipopolysaccharide‐induced inflammation through TLR4/MyD88/NF‐κB cascades in human mononuclear leukocytes

Shi

Wang³

et al. 2019

Phytotherapy Research

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“…demonstrated that NLRP3 promoter contains a putative NFκB binding site and NFκB inhibition resulted in a significant reduction of NLRP3 expression54. Meanwhile, mounting evidence suggests that NLRP3 inflammasome formation is positively associated with NFκB activity5556. All these findings implied that the pro-tumorigenic ability of NFκB might be attributed to inflammasome activation.…”

Section: Discussionmentioning

confidence: 99%

Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells

Zhou

Dong

Ziyan

et al. 2017

Sci Rep

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Perfluorodecanoic acid (PFDA), a perfluorinated carboxylic acid, presents in the environment and accumulates in human blood and organs, but its association with tumor promotion are not clear. Given that inflammation plays a significant role in the development of gastric malignancies, we evaluated the effects of PFDA on activation of the inflammasome and inflammation regulation in the gastric cell line AGS. When added to cell cultures, PFDA significantly stimulated IL-1β and IL18 secretion and their mRNA levels compared with control cells. By RT-PCR and western-blot we found that up-regulation of NLRP3 were associated with promotion of IL-1β and IL-18 production. Then expression variation of cIAP1/2, c-Rel and p52 were analyzed, the results demonstrated raised mRNA expression in all the tested genes concomitant with enhanced inflammasome activity after exposure to PFDA. Assays with cIAP2 siRNA and NFκB reporter provided additional evidence that these genes were involved in PFDA-induced inflammasome assembly. Furthermore, increased secretion of IL-1β and IL-18 were detected in stomach of PFDA-treated mice, disorganized alignment of epithelial cells and inflammatory cell infiltration were also observed in the stomach tissues upon PFDA treatment. This study reports for the first time that PFDA regulates inflammasome assembly in human cells and mice tissues.

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“…A previous study also demonstrated that NLRP3 promoter contains putative NF-κB binding site and NF-κB inhibition resulted in a significant reduction of NLRP3 expression [39]. Meanwhile, mounting evidence suggested that NLRP3 inflammasome formation is positively associated with NF-κB activity following drug treatment such as LPS, CPT-11, FGF-21, etc [40-42]. All these findings implied that the pro-tumorigenic ability of NF-κB might be attributed to inflammasome activation.…”

Section: Regulation Of Inflammasome Activationmentioning

confidence: 99%

The inflammasome: an emerging therapeutic oncotarget for cancer prevention

Wang

et al. 2016

Oncotarget

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Deregulated inflammation is considered to be one of the hallmarks of cancer initiation and development regulation. Emerging evidence indicates that the inflammasome plays a central role in regulating immune cells and cytokines related to cancer. The inflammasome is a multimeric complex consisting of NOD-like receptors (NLRs) and responds to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli. Several lines of evidence suggests that in cancer the inflammasome is positively associated with characteristics such as elevated levels of IL-1β and IL-18, activation of NF-κB signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process. A number of NLRs, such as NLRP3 and NLRC4 are also highlighted in carcinogenesis and closely correlate to chemoresponse and prognosis. Although conflicting evidence suggested the duplex role of inflammasome in cancer development, the phenomenon might be attributed to NLRs difference, cell and tissue type, cancer stage, and specific experimental conditions. Given the promising role of inflammasome in mediating cancer development, precise elucidation of its signaling network and pathological significance may lead to novel therapeutic options for malignancy therapy and prevention.

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NZ suppresses TLR4/NF-κB signalings and NLRP3 inflammasome activation in LPS-induced RAW264.7 macrophages

Abstract: These results indicated that NZ inhibited the generations of NO and pro-inflammatory cytokines by suppressing TLR4/MyD88/NF-κB pathway, suggesting that NZ could be an effective candidate for ameliorating LPS-induced inflammatory responses.

Cited by 102 publications

References 35 publications

Isoforskolin and forskolin attenuate lipopolysaccharide‐induced inflammation through TLR4/MyD88/NF‐κB cascades in human mononuclear leukocytes

Isoforskolin and forskolin attenuate lipopolysaccharide‐induced inflammation through TLR4/MyD88/NF‐κB cascades in human mononuclear leukocytes

Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells

The inflammasome: an emerging therapeutic oncotarget for cancer prevention

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