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

Abstract

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.

Protective effect of pyrrolidine dithiocarbamate on isoniazid/rifampicin‑induced liver injury in rats

“…These results indicated that the nF-κB-mediated upregulation of TnF-α may be involved in the pathogenesis of inH/riF-induced liver injury. Several studies have shown that PdTc can prevent inflammatory injury via the inhibition of nF-κB and the subsequent downregulation of TnF-α (27,33). in the present study, it was found that the administration of PdTc reduced inflammation, suppressed NF-κB activation and resulted in the downregulation of TnF-α mrna, indicating that the anti-inflammatory action of PDTC partially contributed to liver protection.…”

The Effects of NF-kB Inhibition with p65-TMD-Linked PTD on Inflammatory Responses at Peri-implantitis Sites

“…The effects of NF-kB inhibition specifically in peri-implantitis were reported in He Cy et al The study used a canine model of ligature-induced peri-implantitis and inhibited NF-kB with pyrrolidine dithiocarbamate (PDTC). The suppression of NF-kB reduced TLR4 protein expression, IL-1, IL-6, IL-8, and TNF-α production, periodontal ligament fibroblasts (PDLFs) apoptosis and induced PDLF proliferation [ 16 ].…”

Immune response of macrophages on super-hydrophilic TiO2nanotube arrays

“…24 , 48 Briefly, macrophages could be induced into the M2 phenotype by the presence of arginine–glycine–aspartic acid (RGD) cell-binding sites in adsorbed Fn, while interaction with P1/P2 segments in absorbed Fg resulted in the generation of M1 phenotypes. 27 , 49 Hydrophilic surfaces facilitated the RGD exposure of adsorbed Fn but hindered the P1/P2 segment exposure of adsorbed Fg, 48 leading to a potentially preferential activation of macrophages toward the M2 phenotype and a modulatory effect on cytokine secretion. Therefore, the super-hydrophilic properties of H 2 -TNT surface may alter the behavior of absorbed proteins, which ultimately regulated macrophage cytokine production to reduce extended pro-inflammatory factor release and promote tissue regeneration.…”