Immunopharmacology and Immunotoxicology最新文献

{"title":"Protective effect of modafinil in bisphenol A-induced lung injury in rats: roles of SIRT1-dependent signaling pathways.","authors":"Walaa Yehia Abdelzaher, Marwa Hassan, Nashwa Fathy Gamal El-Tahawy, Abdel Hamid Sayed AboBakr Ali, DoaaMohamed Elroby Ali, Meriam N N Rezk, Zainab Hassan Saeed, Ayman Geddawy","doi":"10.1080/08923973.2025.2469218","DOIUrl":"10.1080/08923973.2025.2469218","url":null,"abstract":"<p><strong>Background: </strong>Bisphenol A (BPA) is an industrial chemical used in manufacturing epoxy resins, polycarbonate plastics. We aimed to evaluate the possible protective effect of modafinil (MOD) in BPA-induced lung injury.</p><p><strong>Materials and methods: </strong>Twenty-four adult male albino Wistar rats were divided into four groups: Control group, MOD group: rats received modafinil 10 mg/kg/day for 4 weeks, BPA group: rats received Bisphenol A (500 mg/kg/day) for 4 weeks, MOD/BPA group: rats received MOD+ BPA. We measured arterial blood gas (ABG), malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), interlukin-1b (IL-1b), Sirtuin type 1 (SIRT1), Keap1, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), caspase-3 and forkhead-box transcription factor1 (FOXO1) levels, tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) and Heme Oxygenase-1 (HO-1) gene expression. Furthermore; histological changes, interlukin-6 (IL-6) immuno-expression were evaluated.</p><p><strong>Results: </strong>BPA group showed significant increase in the partial pressure of carbon dioxide (PaCO2), MDA, NOx, IL-1b, keap1 and FOXO1, caspase-3 levels; TNF-α and NF-Κb, Bax and HO-1 gene expression, IL-6 exhibited a notable rise in immune-expression in the alveolar wall cells, interstitial cells, and infiltrating inflammatory cells. Moreover; it showed toxic histological changes of marked lung injury. Meanwhile, there is a significant decrease in the partial pressure of oxygen (PaO2), TAC, SIRT1, Nrf2 levels, and Bcl2 gene expression. MOD showed a significant improvement in all parameters.</p><p><strong>Conclusion: </strong>MOD possesses potent ameliorative effects against lung injury caused by BPA <i>via</i> reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"252-262"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics, treatment, and outcomes of nivolumab-induced uveitis.","authors":"Zhaoquan Wu, Wei Sun, Binsheng He, Chunjiang Wang","doi":"10.1080/08923973.2025.2461056","DOIUrl":"10.1080/08923973.2025.2461056","url":null,"abstract":"<p><strong>Background: </strong>Nivolumab has been linked to occurrences of uveitis, yet the clinical features associated with these episodes remain unclear. This study aimed to explore the clinical characteristics of uveitis induced by nivolumab and to offer guidance for its prevention, diagnosis, and treatment.</p><p><strong>Methods: </strong>We conducted a retrospective analysis by gathering case reports related to nivolumab-induced uveitis from both Chinese and English databases, covering the period from inception until 30 September 2024.</p><p><strong>Results: </strong>A total of 38 patients with uveitis were included, with a median age of 63 years (range 35 and 92). The onset of uveitis occurred between 1 week and 24 months post-administration, with a median onset time of 1.4 months. Blurred vision was the primary complaint among patients. Sixteen patients (42.1%) exhibited uveitis resembling Vogt-Koyanagi-Harada (VKH) disease. Bilateral uveitis was the most prevalent form (89.2%), followed by unilateral uveitis (8.1%). Anterior uveitis was the most frequently observed type (52.6%), succeeded by posterior uveitis (23.7%), panuveitis (21.1%), and intermediate uveitis (2.6%). Uveitis showed significant improvement or resolution following treatment with topical or systemic corticosteroids, with a median improvement time of 4 weeks post-therapy.</p><p><strong>Conclusions: </strong>Uveitis is a relatively uncommon adverse effect of nivolumab, typically manifesting within 5 months of treatment. Prompt recognition of nivolumab-induced uveitis and appropriate management are crucial, as most cases are treatable.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"222-227"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case report of carboxymethylcellulose allergy: exploring tolerance based on administration route.","authors":"Anays Piotin, Anh Poirot, Maxence Wurm, Celine Lutz, Naji Khayath, Frédéric de Blay, Carine Metz-Favre","doi":"10.1080/08923973.2025.2469214","DOIUrl":"10.1080/08923973.2025.2469214","url":null,"abstract":"<p><strong>Background: </strong>The management of hypersensitivity to excipients and food additives remains a significant issue for healthcare professionals and patients. Avoiding carboxymethylcellulose (CMC) can be a considerable challenge for patients allergic to CMC due to its widespread use. We assessed the tolerance of CMC through different route of administration in a patient with a confirmed CMC allergy. We conducted a literature review to analyze all relevant cases of patients allergic to CMC, focusing on tolerance through non-injectable routes.</p><p><strong>Methods: </strong>Skin tests, basophil activation tests, oral and nasal provocation tests with CMC were performed to evaluate patient's hypersensitivity.</p><p><strong>Results: </strong>Skin tests and basophil activation tests with CMC were positive and confirmed IgE-mediated hypersensitivity to CMC in the patient. While the patient tolerated oral administration of CMC and CMC-containing eye drops, nasal provocation test resulted in asthma exacerbation and rhinitis.</p><p><strong>Conclusion: </strong>Tolerance of CMC appears to be route-dependent. Provocation tests with CMC through various routes of administration are essential for assessing tolerance and providing appropriate recommendations for patients with CMC allergy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"234-238"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial liver support systems bridge severe immune-mediated hepatotoxicity to clinical recovery.","authors":"Qiangfeng Wang, Cheng Xiao, Peipei Hu, Xiuming Zhang, Jiangshan Lian, Xingyun Su, Xiongfei Yu, Jiajia Chen, Yulong Zheng","doi":"10.1080/08923973.2025.2454030","DOIUrl":"10.1080/08923973.2025.2454030","url":null,"abstract":"<p><strong>Background: </strong>The incidence of hepatic immune-related adverse events has increased with the wide use of immune checkpoint inhibitors (ICIs), some immune-mediated hepatotoxicity (IMH) cases are severe and lack of clinical recommendations.</p><p><strong>Objective: </strong>This study aimed to evaluate the efficacy of artificial liver support systems (ALSSs) in the treatment of IMH.</p><p><strong>Methods: </strong>This retrospective case series included six patients with grade 4 hepatotoxicity with high bilirubin induced by ICIs treated between 1 January 2019 and 31 December 2021. All patients received ALSS treatment.</p><p><strong>Results: </strong>After treatment and recovery, four of the six patients experienced improvement in hepatotoxicity, with total bilirubin (TBIL) levels reduced to ≤ grade 2, and two patients achieved complete recovery (TBIL grade = 0).</p><p><strong>Conclusion: </strong>ALSS serve as a therapeutic option for severe IMH.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"194-200"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vildagliptin attenuates doxorubicin-induced hepatotoxicity via activating Nrf2/HO-1 and SIRT1 and suppressing NF-κB signals in rats.","authors":"Heba M Mahmoud, Emad H M Hassanein, Marwa M Khalaf","doi":"10.1080/08923973.2025.2482863","DOIUrl":"https://doi.org/10.1080/08923973.2025.2482863","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is an anticancer commonly employed in cancer treatment. However, the clinical application of DOX is associated with hepatotoxicity. Vildagliptin is an anti-hyperglycemic agent that inhibits the dipeptidyl peptidase-4 enzyme. Besides being used in managing type-2 diabetes, vildagliptin showed potential anti-inflammatory, antioxidant, and other activities.</p><p><strong>Objective: </strong>Our investigation targeted the hepatoprotective effects of vildagliptin against DOX-induced hepatotoxicity.</p><p><strong>Methods: </strong>Vildagliptin was given in a dose of 30 mg/kg, once daily; p.o. for 2 weeks while DOX was injected in a single dose of 30 mg/kg, i.p.</p><p><strong>Results: </strong>Vildagliptin effectively decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, while it effectively elevated serum total protein (TP) level. Histologically, vildagliptin administration resulted in significant hepatoprotective efficacy with abundant figures of normal hepatocytes. Moreover, vildagliptin considerably decreased lipid peroxidation biomarker malondialdehyde (MDA), and the cytokines interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2, while it remarkably boosted the antioxidative defenses of glutathione (GSH) and catalase (CAT). Dual antioxidant and anti-inflammatory activities were mediated by upregulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2), silent information regulator 1 (SIRT1), and heme oxygenase (HO-1) and suppressing the nuclear factor kappa B (NF-κB) signals. Finally, vildagliptin alleviated apoptosis by downregulating hepatic p53 and cytochrome (Cyt)-C.</p><p><strong>Conclusion: </strong>Our findings suggest that vildagliptin improved hepatocellular architecture and reduced hepatic oxidative injury, inflammation, and apoptosis associated with DOX treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D and canagliflozin combination alleviates Parkinson's disease in rats through modulation of RAC1/NF-κB/Nrf2 interaction.","authors":"Sara Kamal Rizk, Eman A Ali, AlZahraa A M Sheref, Sara G Tayel, Sara A El Derbaly","doi":"10.1080/08923973.2025.2481849","DOIUrl":"https://doi.org/10.1080/08923973.2025.2481849","url":null,"abstract":"<p><strong>Objective: </strong>Oxidative stress and neuroinflammation are crucial factors in the pathogenesis of Parkinson's disease (PD). Vitamin D (Vit D) and canagliflozin (CAN) are known to have anti-inflammatory and antioxidant properties. Together, they target key molecular pathways involved in PD, including oxidative stress and neuroinflammation, specifically, the small GTPase protein (RAC1)/nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which regulates brain's oxidative stress and inflammation. This study investigates the effects of Vit D and CAN alone and in combination in a rat model of PD.</p><p><strong>Materials and methods: </strong>Fifty male Wistar rats were assigned to five groups (<i>n</i> = 10), including control, rotenone (ROT), Vit D + ROT, CAN + ROT, and Vit D + CAN + ROT. We assessed weight changes, brain weight, neurobehavioral functions, biochemical markers, and immunohistopathology of brain tissues.</p><p><strong>Results: </strong>The results showed that Vit D treatment was more effective than CAN in alleviating PD symptoms, with the combination of Vit D and CAN offering the best therapeutic outcome. This combination therapy significantly improved serum Vit D, striatal dopamine (DA) levels, antioxidant status (reduced glutathione (GSH) and catalase (CAT), reduced oxidative stress (malondialdehyde (MDA)), and ameliorated inflammation (tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10)). Additionally, the combination therapy modulated the expression of RAC1, NF-κB, Nrf2, vitamin D receptors (VDR), and vitamin D-binding protein (DBP) and immunoexpression of tyrosine hydroxylase (TH), and α-synuclein (α-SYN).</p><p><strong>Conclusion: </strong>These findings suggest that Vit D and CAN synergistically modulate the RAC1/NF-κB/Nrf2 pathway, leading to improved neuroprotection in PD.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of roflumilast on cyclophosphamide-induced ovarian toxicity in rats: role of SIRT1/Nrf2/nF-ĸB pathway.","authors":"Salma A El-Marasy, Hadir Farouk, Marwa S Khattab, Marwan Abdelbaset","doi":"10.1080/08923973.2025.2482804","DOIUrl":"https://doi.org/10.1080/08923973.2025.2482804","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the possible protective effect of roflumilast (RFL) on cyclophosphamide (CP)-induced ovarian toxicity as well as the possible underlying mechanism.</p><p><strong>Material and methods: </strong>Female Wistar rats received the vehicle (<i>n</i> = 6) or CP (200 mg/kg, i.p.). The other 2 groups (<i>n</i> = 6 for each) were orally pretreated with RFL at dosages of 0.5 and 1 mg/kg, respectively, for 14 days and then after one hour of RFL administration on the 14th day, rats were intraperitoneally administered a single dose of CP. Serum and tissue samples were collected. Biochemical, real-time polymerase chain reaction, histopathological and immunohistopathological examination were carried out.</p><p><strong>Results: </strong>RFL significantly elevated serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) compared to the CP group. RFL remarkably elevated ovarian contents of Sirtuin-1 (SIRT1), heme oxygenase-1 (HO-1), and reduced nuclear factor-kappa B (NF-ĸb) p65/NF-ĸB ratio as compared to control CP group. Compared to the CP group, RFL significantly elevated Nrf2 gene expression, reduced malondialdehyde (MDA), and elevated the reduced glutathione (GSH) ovarian content. It also reduced the protein expression of TNF-α and caspase-3.</p><p><strong>Conclusion: </strong>It can be concluded that RFL (0.5 and 1 mg/kg) protected rats against CP-induced ovarian toxicity <i>via</i> altering the SIRT1/Nrf2/NF-ĸB pathway, ameliorating histopathological changes in addition to its anti-apoptotic effect.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory effects of vitamin B6 on neuroinflammation and neuronal damage caused by 1,2-diacetylbenzene in BV2 microglial and sH-SY5Y cells.","authors":"Hai Duc Nguyen, Won Hee Jo, Ngoc Hong Minh Hoang, Min-Sun Kim","doi":"10.1080/08923973.2025.2469216","DOIUrl":"https://doi.org/10.1080/08923973.2025.2469216","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiology of cognitive impairment has recently focused on 1,2-Diacetylbenzene (DAB), B vitamins, tau hyperphosphorylation, and neuroinflammation. While past evidence shows that vitamin B6 influences the immune system, the molecular processes behind DAB-induced neuroinflammation and cognitive impairment remain largely unknown. This study aimed to assess the protective roles of vitamin B6 against DAB-induced toxicity in BV2 microglial and SH-SY5Y cells.</p><p><strong>Methods: </strong><i>In vitro</i> approaches included Western blot, qRT-PCR, cell viability assays, immunocytochemistry, reactive oxygen species, and nitrite assays. For <i>in silico</i> analysis, we utilized Metascape, Cytoscape, MIENTURNET, and molecular docking.</p><p><strong>Results: </strong>Vitamin B6 suppressed the TLR4/NF-κB pathway and the TREM-1/DAP12/NLRP3/caspase-1/IL1B pathway in DAB-activated BV2 cells. Additionally, it reduced reactive oxygen species and nitric oxide levels while increasing Nrf2 and IL10 production. In SH-SY5Y cells, vitamin B6 inhibited GSK-3β Tyr216, tau hyperphosphorylation, and β-amyloid production. The <i>in silico</i> analysis identified 'positive regulation of NF-κB transcription factor activity,' 'regulation of IL-6 production,' and 'positive regulation of adaptive immune response' as key molecular mechanisms linked with DAB-induced cognitive impairment and targeted by vitamin B6. Core genes, miRNAs, and transcription factors included IL1β, IL6, IL10, TNF, hsa-miR-155-5p, hsa-miR-203a-3p, hsa-miR-106a-5p, hsa-miR-26a-5p, CEBPB, and PXR.</p><p><strong>Conclusion: </strong>Our findings indicate that vitamin B6 may protect against DAB-induced cognitive impairment by attenuating key inflammatory pathways, reducing oxidative stress, and inhibiting tau hyperphosphorylation, β-amyloid production, and GSK-3β Tyr216 phosphorylation. This highlights its potential as a therapeutic agent for cognitive impairment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.9,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The protective effects of a single dose myricetin application on CLP-induced rat sepsis model by analyzing some immune mechanisms.","authors":"Ismail Can, Ali Guraslan, Omer Faruk Baser, Gulfem Nur Yıldız, Ihsan Toplaoglu, Selina Aksak Karamese, Murat Karamese","doi":"10.1080/08923973.2025.2469227","DOIUrl":"10.1080/08923973.2025.2469227","url":null,"abstract":"<p><strong>Introduction: </strong>In this study, our aim was to investigate the protective effects of myricetin (single dose-100 mg/kg) on CLP-induced rat sepsis model by analyzing some immune mechanisms including inflammation and oxidative stress by different techniques such as Immunohistochemistry, ELISA, tissue biochemistry and Western Blotting.</p><p><strong>Methods: </strong>Twenty-eight Wistar albino rats were divided into 4 groups. The pro-inflammatory and anti-inflammatory cytokine levels were measured by ELISA technique. CD68 and Nuclear-Factor-Kappa-B (NF-κB) positivity rates were detected by IHC. Some of oxidative stress parameters were measured by tissue biochemistry, while Toll-like receptor-4 (TLR4) expression others were detected by Western blot technique.</p><p><strong>Results: </strong>Sepsis caused a significant increase in all pro-inflammatory cytokine and oxidant levels. Also, it led to an increase in the positivity of CD68 and NF-κB markers as well as the expression levels of TNF-alpha, IL-1-beta, TLR4, Keap-1. However, single dose myricetin application normalized pro-inflammatory cytokine levels, increased anti-oxidant and anti-inflammatory cytokine levels, decreased positivity of CD68 and NF-κB and increased NRF2 and HO-1 expressions.</p><p><strong>Discussion: </strong>As a conclusion, the beneficial effect of myricetin on lung injury also involved inhibition of TLR4/NF-κB pathway, suppression of proinflammatory cytokines and induction of anti-inflammatory cytokine production, regulation of oxidant and anti-oxidant system parameters, and activating the NRF2/Keap1/HO-1 pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Punicalagin ameliorates lipopolysaccharide-induced inflammatory response in dental pulp cells via inhibition of the NF-κB/Wnt5a-ROR2 pathway.","authors":"Yumeng Yang, Ke Deng, Shan Jiang, Xiaolan Guo, Yiming Zhong, Buling Wu, Liu Wei","doi":"10.1080/08923973.2025.2470343","DOIUrl":"10.1080/08923973.2025.2470343","url":null,"abstract":"<p><strong>Introduction: </strong>Punicalagin (PCG) is a major polyphenolic component with potent anti-inflammatory, anti-atherogenic, anti-cancer, and antioxidant activities. This study aimed to investigate the impact and underlying mechanisms of PCG on lipopolysaccharide (LPS)-induced dental pulpitis.</p><p><strong>Methods: </strong>A rat pulpitis model was constructed, and the infected pulp was covered with a PCG collagen sponge. <i>In vitro</i>, dental pulp cells (DPCs) were isolated, and the effects of LPS and PCG on cell viability were assessed. The expression levels of inflammation-related factors were investigated by qRT-PCR and ELISA. The Nuclear Factor kappa B (NF-κB) transcription factors and Wnt family member 5a-Receptor tyrosine kinase like Orphan Receptor 2 (Wnt5a-ROR2) levels were evaluated by immunofluorescence staining and Western blotting.</p><p><strong>Results: </strong>We demonstrated that the PCG collagen sponge effectively reduced the infiltration of inflammatory cells in the pulp. PCG significantly alleviated the inflammatory response by reducing the mRNA expression levels of IL-1β, IL-6, IL-8, ICAM-1, and VCAM-1 and the secretion of IL-6 and IL-8 in a concentration-dependent manner. Immunofluorescence staining showed that the activation of the NF-κB pathway was hindered by PCG, which affected with the nuclear translocation of P65. PCG reduced the phosphorylation levels of P65 and IκBα and suppressed the expression levels of Wnt5a and ROR2 induced by LPS. The NF-κB inhibitor Bay11-7082 reduced the activation of the NF-κB/Wnt5a-ROR2 pathway and the inflammatory response; the application of PCG significantly augmented this inhibitory effect.</p><p><strong>Discussion: </strong>PCG demonstrated an anti-inflammatory effect in LPS-induced DPCs by targeting the NF-κB/Wnt5a-ROR2 signaling pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}