The role of TLR4-mediated PTEN/PI3K/AKT/NF-κB signaling pathway in neuroinflammation in hippocampal neurons

Zhao, Min; Zhang, Ailing; Xu, Long; Zhang, X.

doi:10.1016/j.neuroscience.2014.03.039

Cited by 98 publications

(80 citation statements)

References 27 publications

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“…It has been reported that NF-κB inhibits the proliferation and modulates the progression of lens epithelial cells [49]. In hippocampal neurons, treatment with TLR4 antibody, bpV(pic), or PDTC decreased the LPS-induced nuclear translocation of NF-κB and resulted in the down-regulation of TNF-α and IL-1β expression [50], which revealed that the TLR4-mediated NF-κB signaling pathway is associated with the activation of a neuroinflammatory response. In human acute monocytic leukemia, anti-β2GPI/β2GPI stimulates activation of THP-1 cells (an acute monocytic leukemia cell line) by inducing IL-6, IL-8 and TNF-α expression through the TLR4/MD-2/MyD88 and NF-κB signaling pathways [51].…”

Section: Discussionmentioning

confidence: 87%

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Jiang²,

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The roles of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in peri-implantitis are unclear. Here, we used a canine model of peri-implantitis to explore the effects of inhibiting NF-κB with pyrrolidine dithiocarbamate (PDTC) on the inflammatory response in ligature-induced peri-implantitis. Methods: After successfully establishing the peri-implantitis model, beagles were randomly assigned to normal, model or PDTC groups. ELISA tests were used to determine the levels of interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). Immunohistochemistry was employed to assess the expression of NF-κB p65. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the mRNA levels of TLR4 and NF-κB p65, and western blot analysis was used to measure the protein levels of TLR4 in periodontal tissues from each group. Periodontal ligament fibroblasts (PDLFs) were cultured and subsequently classified into PDLF normal, PDLF model, PDLF LPS, PDLF PDTC, and PDLF LPS + PDTC groups. An immunofluorescence assay was used to measure the expression level of NF-κB p65. The CCK-8 assay and flow cytometry were performed to evaluate cell proliferation and apoptosis. Results: The in vitro results indicated that NF-κB p65 and TLR4 were upregulated in canine periodontal tissues, and PDTC could suppress the expression levels of NF-κB p65 and TLR4. Inflammation could increase TLR4 protein expression in canine periodontal tissue, and PDTC could inhibit the inflammation-induced increase in TLR4 protein expression. These results revealed that PDTC could reverse the LPS-induced increases in the levels of IL-1, IL-6, IL-8 and TNF-α. In vivo, the results demonstrated that PDTC inhibited the LPS-induced NF-κB p65 upregulation, and PDTC could reverse the inhibitory effect of the PDLF model + LPS on the proliferation of periodontal fibroblasts. The results also showed that in the PDLF model, LPS promoted PDLF apoptosis by inducing implant periodontitis in canines, but PDTC inhibited the PDLF apoptosis and relieved implant periodontitis in canines. Conclusion: Based on our results, we concluded that PDTC can inhibit the expression of NF-κB and alleviate the inflammatory response induced by LPS, thereby preventing periodontal inflammation and reducing the development of peri-implantitis.

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Section: Discussionmentioning

confidence: 87%

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Jiang²,

Wang

et al. 2018

Cell Physiol Biochem

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“…NF-κB is known to be an important nuclear transcription factor, and plays a predominant role in cell innate immune system [56,57,58]. It has been reported to play central roles in inflammatory response to mycoplasma invasion [4,59,60].…”

Section: Discussionmentioning

confidence: 99%

“…Activation of NF-κB depends on the phosphorylation of IκB kinase-α via the PI3K/AKT pathway [62,63]. PI3K/AKT/NF-κB constitutes an important signaling pathway in regulating inflammatory response and cell functions [57,64]. Given the importance of NF-κB in inflammatory response to MG and the significant regulatory effect of PI3K and AKT on NF-κB-mediated inflammatory pathway, we further investigate the effect of miR-130b-3p on NF-κB expression.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

Yuan

Zou

Zhao

et al. 2018

IJMS

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Mycoplasma gallisepticum (MG) is the pathogen of chronic respiratory disease (CRD), hallmarked by vigorous inflammation in chickens, causing the poultry industry enormous losses. miRNAs have emerged as important regulators of animal diseases. Previous miRNA sequencing data has demonstrated that miR-130b-3p is up-regulated in MG-infected chicken embryo lungs. Therefore, we aimed to investigate the function of miR-130b-3p in MG infection of chickens. RT-qPCR results confirmed that miR-130b-3p was up-regulated both in MG-infected chicken embryo lungs and chicken embryonic fibroblast cells (DF-1 cells). Furthermore, functional studies showed that overexpression of miR-130b-3p promoted MG-infected DF-1 cell proliferation and cell cycle, whereas inhibition of miR-130b-3p weakened these cellular processes. Luciferase reporter assay combined with gene expression data supported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) was a direct target of miR-130b-3p. Additionally, overexpression of miR-130b-3p resulted in up-regulations of phosphatidylinositol-3 kinase (PI3K), serine/threonine kinase (AKT), and nuclear factor-κB (NF-κB), whereas inhibition of miR-130b-3p led to the opposite results. Altogether, upon MG infection, up-regulation of miR-130b-3p activates the PI3K/AKT/NF-κB pathway, facilitates cell proliferation and cell cycle via down-regulating PTEN. This study helps to understand the mechanism of host response to MG infection.

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“…The activation signal diverges, following either of two independent inflammatory cascades, the MyD88 (myeloid differentiation primary response gene 88) pathway to NF-jB activation or the TRIF (TIR-domain-containing adapter-inducing interferon-b) pathway for the cytoplasmic Toll/ IL-1 receptor-containing adaptor, to induce interferon (IFN)-b production. Activation of the PI3K (phosphatidylinositol-3-kinase)/ AKT signaling pathway was recently indicated as an important step toward NF-jB activation and cytokine release by LPS in microglial cells and hippocampal neurons (Saponaro et al, 2012;Zhao et al, 2014); furthermore, a role for AMPK in modulating the LPS inflammatory response in the brain was previously suggested (Giri et al, 2004;Labuzek et al, 2010). However, this point remains controversial, since LPS seems to increase pAMPK while the ribonucleotide analog AICAR, an AMPK activator, inhibits pro-inflammatory responses elicited by LPS in vitro (Ayasolla et al, 2005).…”

Section: Lps Mtor Cytokines and Neuroinflammationmentioning

confidence: 99%

Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release

Russo

Andreozzi

Iuliano

et al. 2014

Brain, Behavior, and Immunity

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The role of TLR4-mediated PTEN/PI3K/AKT/NF-κB signaling pathway in neuroinflammation in hippocampal neurons

Cited by 98 publications

References 27 publications

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Inhibition of NF-κB by Pyrrolidine Dithiocarbamate Prevents the Inflammatory Response in a Ligature-Induced Peri-Implantitis Model: A Canine Study

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release

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