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

2018 ◽  
Vol 49 (2) ◽  
pp. 610-625 ◽  
Author(s):  
Chun-Yan He ◽  
Li-Peng Jiang ◽  
Cheng-Yue Wang ◽  
Yue Zhang
Keyword(s):  
Inflammatory Response ◽  
Protein Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Pyrrolidine Dithiocarbamate ◽  
Mrna Levels ◽  
Periodontal Ligament Fibroblasts ◽  
Necrosis Factor Alpha ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Tnf Α

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.

scholarly journals Levels of Gene Expression of Immunological Biomarkers in Peri-Implant and Periodontal Tissues

2020 ◽  
Vol 17 (23) ◽  
pp. 9100
Author(s):  
Luciene Cristina Figueiredo ◽  
Bruno Bueno-Silva ◽  
Cristiana Fernandes Plutarco Nogueira ◽  
Leonardo Carneiro Valadares ◽  
Katia Marina Morilla Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteases ◽  
Gingival Tissue ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Periodontal Tissues ◽  
Tnf Α ◽  
The Matrix ◽  
Study Population ◽  
Factor Alpha

This study compared the gene expression of the immunoinflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor alpha (TNF-α), the matrix metalloproteinases (MMP)-1, -2, -8, and -9, and the tissue inhibitors of matrix metalloproteases (TIMP)-1 and -2 in the gingival tissue of individuals with periodontal and peri-implant disease. The study population included individuals with four periodontal statuses: periodontal health (PH group, n = 20); periodontitis (P group, n = 20); peri-implant health (PIH group, n = 20), and peri-implantitis (PI group, n = 20). Gingival biopsies were collected from one tooth per patient according to the inclusion criteria of each group. The mRNA levels of IL-6, IL-1ß, TNF-α, MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were evaluated by qPCR. The levels of IL-1ß were significantly higher in the PI group when compared to the other groups (p < 0.05), while the levels of IL-6 were significantly higher in the groups with periodontal and peri-implant disease when compared with the healthy groups (p < 0.05); however, the levels of IL-6 did not differ between the PI and P groups (p > 0.05). For all other studied biomarkers, no significant differences were observed between groups (p > 0.05). IL-6 and IL-1ß presented higher levels of mRNA in diseased periodontal and peri-implant tissues. However, the expression of metalloproteinases and their inhibitors did not differ between the different periodontal statuses.

scholarly journals Antioxidant glutathione inhibits inflammation in synovial fibroblasts via PTEN/PI3K/AKT pathway: An in vitro study

2021 ◽  
Author(s):  
Wen Ting Hao ◽  
Lu Huang ◽  
Wei Pan ◽  
Yi Le Ren
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
In Vitro Study ◽  
Synovial Fibroblasts ◽  
Akt Pathway ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Messenger Ribonucleic Acid ◽  
Tnf Α

Objectives: In this study, we aimed to investigate whether glutathione (GSH) could decrease the secretion of reactive oxygen species (ROS), reduce inflammation, and modulate the phosphatase and tensin homolog deleted on chromosome 10/phosphatidylinositol 3-kinase/AKT (PTEN/PI3K/AKT) in synovial fibroblasts (SFs). Patients and methods: A total of 30 DBA/1J female mice were used in this study. The release of ROS in MH7A cells was examined using a ROS assay kit. The effects of GSH on the messenger ribonucleic acid (mRNA) expression and protein levels of inflammatory cytokines were determined via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) in mouse SFs and MH7A cells, respectively. The PTEN/PI3K/AKT pathway was investigated via Western blotting. The effects of buthionine-sulfoximine (BSO), as an inhibitor of GSH, on these molecules were examined. Results: The ROS were decreased after GSH treatment, and the mRNA levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-1, MMP-3, were also significantly inhibited after GSH stimulation. However, the IL-10 levels were enhanced, and GSH increased the expression of PTEN. The GSH suppressed the activation of phosphorylated (p)-PI3K and p-AKT. The supplementation of the BSO restored the activation of PI3K/AKT pathway with a high production of ROS. The levels of TNF-α, IL-1β and IL-6 were also elevated, when the BSO was added. Conclusion: These findings suggest that GSH can act as an inflammatory suppressor by downregulating the PTEN/PI3K/AKT pathway in MH7A cells. These data indicated a novel function of GSH for improving the inflammation of RA SFs and may help to alleviate the pathological process of RA.

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

scholarly journals The Inflammatory Response Induced by Aspartic Proteases of Candida albicans Is Independent of Proteolytic Activity

2010 ◽  
Vol 78 (11) ◽  
pp. 4754-4762 ◽  
Author(s):  
Donatella Pietrella ◽  
Anna Rachini ◽  
Neelam Pandey ◽  
Lydia Schild ◽  
Mihai Netea ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inflammatory Response ◽  
Proteolytic Activity ◽  
Necrosis Factor Alpha ◽  
Pathogenic Yeast ◽  
Aspartic Proteases ◽  
Akt Activation ◽  
Tnf Α ◽  
Factor Alpha ◽  
Pepstatin A

ABSTRACT The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast Candida albicans. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca2+ influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of C. albicans with the host.

scholarly journals Upregulation of Cytokines Is Detected in the Placentas of Cattle Infected with Neospora caninum and Is More Marked Early in Gestation When Fetal Death Is Observed

2008 ◽  
Vol 76 (6) ◽  
pp. 2352-2361 ◽  
Author(s):  
Anne Rosbottom ◽  
E. Helen Gibney ◽  
Catherine S. Guy ◽  
Anja Kipar ◽  
Robert F. Smith ◽  
...  
Keyword(s):  
Protein Expression ◽  
Fetal Death ◽  
Neospora Caninum ◽  
Late Gestation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Cytokine Mrna ◽  
Early Gestation ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-γ), IL-12p40, tumor necrosis factor alpha (TNF-α), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4+ T cells and macrophages. IFN-γ protein expression was also highly increased, and a modest increase in transforming growth factor β was detected. A much smaller increase in the same cytokines and IFN-γ protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-α, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle.

Abstract 393: Anti-inflammatory Properties of Aqueous Extracts of Sesame Oil

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Krithika Selvarajan ◽  
Chandrakala Aluganti Narasimhulu ◽  
Reena Bapputty ◽  
Sampath Parthasarathy
Keyword(s):  
Protein Expression ◽  
Aqueous Extract ◽  
Dietary Intervention ◽  
Sesame Oil ◽  
Luciferase Assay ◽  
Treatment Modalities ◽  
Raw 264.7 Cells ◽  
Mrna Levels ◽  
Tnf Α ◽  
Anti Inflammatory

Background Dietary intervention to prevent atherosclerosis and inflammation has been a major focus in recent years. Sesame oil (SO), widely used in many Asian countries, has been reported to help reduce high blood pressure. It has also been shown to reduce plasma cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride levels. We previously reported that SO was effective in inhibiting atherosclerosis in LDL-receptor negative mice. In this study we tested whether the aqueous, non-lipid components of SO might have anti-inflammatory effects. Methods Sesame oil was extracted using ethanol:water mixture, lyophilized and reconstituted in water. To study anti-inflammatory effect, RAW 264.7 cells (macrophage cell line) were treated with the aqueous extract in the presence or absence of lipopolysaccharide (LPS) for 24 hours. RNA was extracted using Trizol. mRNA expression of inflammatory cytokines such as IL-1α, IL-6 and TNF-α were analyzed by real time PCR. Protein expression was determined by western blot analysis. To identify the mechanism of action, we performed luciferase assay using HepG2-LXR reporter cell lines. Results LPS induced the expression of IL-1α, IL-6 and TNF-α mRNA levels in RAW cells. The extract alone did not significantly affect the expressions of inflammatory cytokine genes. However, when treated together with LPS, sesame oil aqueous extract inhibited the mRNA levels of these cytokines significantly. Treatment with LPS together with SO extract also decreased the protein expression of these cytokines. The SO extract induced LXR expression as identified by the luciferase assay system in HepG2-LXR reporter cells. Conclusion These findings suggest that the aqueous portion of SO might be effective in preventing inflammation. Furthermore, the activation of LXR might suggest additional effects on lipid metabolism. Identifying the specific components present in the aqueous extract will be instrumental in developing treatment modalities for atherosclerosis and other inflammatory conditions.

scholarly journals Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yan Chen ◽  
Yan-Jun Wang ◽  
Ying Zhao ◽  
Jin-Cheng Wang
Keyword(s):  
Diabetes Mellitus ◽  
Inflammatory Response ◽  
Mesangial Cells ◽  
Binding Protein ◽  
The Body ◽  
Mrna Levels ◽  
Diabetic Mice ◽  
Response Element ◽  
Tnf Α ◽  
Element Binding Protein

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.

Oxymatrine inhibits lipopolysaccharide-induced inflammation by down-regulating Toll-like receptor 4/nuclear factor-kappa B in macrophages

2015 ◽  
Vol 93 (4) ◽  
pp. 253-260 ◽  
Author(s):  
Yu Zhang ◽  
Ruhong Yan ◽  
Yae Hu
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Chinese Herb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Anti Inflammatory

Oxymatrine (OMT) is the quinolizidine alkaloid extracted from the Chinese herb Sophora flavescens Ait. that has many pharmacological effects and is used for the treatment of some inflammatory diseases. In this study, RAW264.7 cells and THP-1 differentiated macrophages were pretreated with various concentrations of OMT at 2 h prior to treatment with lipopolysaccharide (LPS) (1.0 μg/mL) for different durations. We detected the anti-inflammatory effect of OMT in LPS-stimulated macrophages and investigated the molecular mechanism. We showed that OMT pretreatment significantly inhibited the LPS-induced secretion of nitric oxide (NO), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) in supernatant, attenuated the mRNA levels of inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and Toll-like receptor 4 (TLR4), increased TLR4 and phosphorylation of inhibitor of kappa B-alpha (p-IBα) in cytosol, and decreased the nuclear level of nuclear factor-κB (NF-κB) p65 in macrophages. In conclusion, OMT exerts anti-inflammatory properties in LPS-stimulated macrophages by down-regulating the TLR4/NF-κB pathway.

scholarly journals Enterococcus faecalisDemonstrates Pathogenicity through Increased Attachment in anEx VivoPolymicrobial Pulpal Infection

2018 ◽  
Vol 86 (5) ◽  
Author(s):  
Wayne Nishio Ayre ◽  
Genevieve Melling ◽  
Camille Cuveillier ◽  
Madhan Natarajan ◽  
Jessica L. Roberts ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Host Response ◽  
Ex Vivo ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Streptococcus Anginosus ◽  
Cell Counts ◽  
Tnf Α ◽  
Factor Alpha ◽  
Infection Types

ABSTRACTThis study investigated the host response to a polymicrobial pulpal infection consisting ofStreptococcus anginosusandEnterococcus faecalis, bacteria commonly implicated in dental abscesses and endodontic failure, using a validatedex vivorat tooth model. Tooth slices were inoculated with planktonic cultures ofS. anginosusorE. faecalisalone or in coculture atS. anginosus/E. faecalisratios of 50:50 and 90:10. Attachment was semiquantified by measuring the area covered by fluorescently labeled bacteria. Host response was established by viable histological cell counts, and inflammatory response was measured using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. A significant reduction in cell viability was observed for single and polymicrobial infections, with no significant differences between infection types (∼2,000 cells/mm2for infected pulps compared to ∼4,000 cells/mm2for uninfected pulps).E. faecalisdemonstrated significantly higher levels of attachment (6.5%) thanS. anginosusalone (2.3%) and mixed-species infections (3.4% for 50:50 and 2.3% for 90:10), with a remarkable affinity for the pulpal vasculature. Infections withE. faecalisdemonstrated the greatest increase in tumor necrosis factor alpha (TNF-α) (47.1-fold forE. faecalis, 14.6-fold forS. anginosus, 60.1-fold for 50:50, and 25.0-fold for 90:10) and interleukin 1β (IL-1β) expression (54.8-fold forE. faecalis, 8.8-fold forS. anginosus, 54.5-fold for 50:50, and 39.9-fold for 90:10) compared to uninfected samples. Immunohistochemistry confirmed this, with the majority of inflammation localized to the pulpal vasculature and odontoblast regions. Interestingly,E. faecalissupernatant and heat-killedE. faecalistreatments were unable to induce the same inflammatory response, suggestingE. faecalispathogenicity in pulpitis is linked to its greater ability to attach to the pulpal vasculature.

Corydalis Saxicola Bunting Total Alkaloids Inhibits Paclitaxel-Induced Peripheral Neuropathy By Regulating PKCε-TRPV1 and p38 MAPK-TRPV1 Signaling Pathways

2021 ◽  
Author(s):  
chu xue ◽  
Si-Xue Liu ◽  
Jie Hu ◽  
Jin Huang ◽  
Hong-Min Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Peripheral Neuropathy ◽  
Protein Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Cell Model ◽  
Mrna Levels ◽  
Drg Neurons ◽  
Total Alkaloids ◽  
Tnf Α

Abstract Background: Corydalis saxicola Bunting, a traditional Chinese medicine, has been proven to work well in anti-inflammation, blood circulation improvement, hemostasis, analgesia. This study was designed to observe the effects and potential mechanism of Corydalis saxicola Bunting total alkaloids (CSBTA) on paclitaxel-induced peripheral neuropathy (PIPN). Materials and methods: Following 4 times intraperitoneal injections of paclitaxel (2 mg/kg) and intragastrically (i.g.) administrated at 30 or 120 mg/kg CSBTA, mechanical and thermal allodynia and hyperalgesia in rats were tested. After 40 days, serum was collected for the detection of PGE2, TNF-α, and IL-1β by ELISA. The L4-L6 segment spinal cord, DRG, and plantar skin were harvested, and protein and gene expression of CGRP, SP, TRPV1, p38, and PKCε were analyzed by Western-blot or RT-qPCR. Parallelly, the PIPN cell model was also established in primary DRG neurons by paclitaxel stimulation (300 nM, 5 d). We examined PGE2, TNF-α and CGRP mRNA levels, and the protein expression on the PKCε-TRPV1 and p38 MAPK-TRPV1 pathways in PIPN cell model with or without CSBTA (25 μg/ml and 50 μg/ml). Results: The results showed that CSBTA effectively ameliorated allodynia and hyperalgesia in PIPN rats, regulated the contents of cytokines and neuropeptides in different tissues and cell models. CSBTA significantly decreased the protein expression of PKCε-TRPV1 and p38 MAPK-TRPV1 signaling pathways in the spinal cord and DRG tissues in the PIPN animal model and primary DRG neurons. Conclusion: Therefore, CSBTA has a perspective therapeutic effect on the treatment of paclitaxel-induced peripheral neuropathy.

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