TLR4/NF-κB Signaling Contributes to Chronic Unpredictable Mild Stress-Induced Atherosclerosis in ApoE-/- Mice

Tang, Yunlian; Jiang, Jian Hong; Wang, Shuang; Zhu, Liangliang; Tang, Xiao Qing; Peng, Juan; Yang, Yue; Gu, Hong‐Feng

doi:10.1371/journal.pone.0123685

Cited by 39 publications

(34 citation statements)

References 39 publications

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“…It has been reported that PDTC suppresses the subsequent inflammatory activation [32]. For instance, PDTC has also been shown to decrease the plasma levels of IL-1β and TNF-α in atherosclerotic subjects [33], which is consistent with our findings.…”

Section: Discussionsupporting

confidence: 93%

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: Discussionsupporting

confidence: 93%

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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“…[ 3 ] A correlation among glucocorticoid, chronic inflammation, and chronic-stress-induced AS has been documented. [ 4 5 ] However, most of these experiments used mice (especially apoE-/-mice) as animal models and mainly focused on the effects of stress on total lesion areas rather than on atherosclerotic vascular wall or plaque stability. [ 6 ]…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Chronic Stress-induced Reduced Atherosclerotic Medial Area and Increased Plaque Instability in Rabbit Models of Chronic Stress

Deng

et al. 2018

Chinese Medical Journal

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Background:Chronic stress contributes to increased risks of atherosclerotic diseases including heart disease, stroke, and transient ischemic attack. However, its underline mechanisms are poorly understood. This study aimed to elucidate the mechanism via which chronic stress exerts its effect on atherosclerosis (AS).Methods:Fifty male New Zealand white rabbits were used. Aortic balloon-injury model was applied. Both social stress and physical stress methods were adopted to establish chronic stress models. The lumen stenotic degree, intimal and medial areas, maximum fibrous cap thickness, and plaque contents were measured with histological sections. Proteomic methods were applied to detect protein changes in abdominal aortas to identify the specialized mediators. Real-time reverse transcription-polymerase chain reaction was used for further verification and investigation.Results:The stress rabbits exhibited lower body weight, worse fur state, more inactivity behavior, and higher serum cortisol level. Chronic stress was significantly associated with the decreased medial area and increased plaque instability, which was manifested by thinner fibrous caps, larger lipid cores, more macrophages, and new vessels but fewer smooth muscle cells and elastic fibers. After chronic stress, the apoptosis-related genes UBE2K, BAX, FAS, Caspase 3, Caspase 9, and P53 were upregulated, and BCL-2/BAX was down-regulated; the angiogenesis-related genes ANG and VEGF-A were also highly expressed in atherosclerotic arteries.Conclusions:Rabbit models of chronic stress were successfully established by applying both social stress and physical stress for 8 weeks. Chronic stress can reduce AS tunica media and accelerate plaque instability by promoting apoptosis and neovascularization.

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“…Toll-like receptors (TLRs), critical mediators in inflammatory response, participate in progression of atherosclerotic lesions. 10 TLRs could recruit and stimulate activation of nuclear factor-κB (NF-κB). 11 NF-κB functions as transcriptional factor to regulate genes involved in immune responses and cytokines production.…”

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confidence: 99%

Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates 2,4,6‐trinitrobenzenesulfonic acid‐induced colitis via repressing toll‐like receptor 4/nuclear factor‐kappa B

Lei

Yuan

et al. 2020

The Kaohsiung J of Med Scie

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Inflammatory bowel disease (IBD) is characterized by recurring inflammatory disorders in digestive system, and devoid of effective treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9), stimulated via inflammation whose inhibition could decrease secretion of inflammatory factors. We then determined whether inhibition of PCSK9 could improve the inflammation. First, rats model of colitis was first established via administration of 2,4,6‐trinitrobenzenesulfonic acid (TNBS), and then verified via determination of body weight loss, myeloperoxidase (MPO) activity, and histopathological analysis of colonic damage. Results showed that treatment with TNBS induced a great body weight loss, MPO activity increase, and serious colonic damage, showing an obviously character of IBD. PCSK9 was elevated in TNBS‐induced rats, and PCSK9 inhibition delivered by adenovirus vector increased the body weight, decreased MPO activity, and ameliorated histological change of colon. Second, the protective effect of PCSK9 inhibition against TNBS‐induced colitis was accompanied by decrease of proinflammatory factors secretion, including tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, intercellular adhesion molecule 1, and monocyte chemoattractant protein‐1. TNBS could activate toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐κB) signaling pathway, while PCSK9 inhibition suppressed activation of TLR4/NF‐κB in TNBS‐induced rats. In conclusion, PCSK9 inhibition attenuated TNBS‐induced rat colitis through anti‐inflammatory effect under inactivation of TLR4/NF‐κB, suggesting potential therapeutic strategy in IBD.

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TLR4/NF-κB Signaling Contributes to Chronic Unpredictable Mild Stress-Induced Atherosclerosis in ApoE-/- Mice

Cited by 39 publications

References 39 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

Mechanism of Chronic Stress-induced Reduced Atherosclerotic Medial Area and Increased Plaque Instability in Rabbit Models of Chronic Stress

Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates 2,4,6‐trinitrobenzenesulfonic acid‐induced colitis via repressing toll‐like receptor 4/nuclear factor‐kappa B

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