Immunopharmacology and Immunotoxicology最新文献

{"title":"PF127/bleomycin hydrogel promotes subcutaneous extracellular matrix remodeling and fibrosis to construct personalized flaps through the TGFβ-Col signaling pathway.","authors":"Zhicheng Sun, Chengxiong Huang, Zheming Cao, Yu Xiao, Panfeng Wu, Xiaoyang Pang, Yan Yang","doi":"10.1080/08923973.2024.2393217","DOIUrl":"10.1080/08923973.2024.2393217","url":null,"abstract":"<p><strong>Background: </strong>Skin flap transplantation is used to effectively reconstruct defects of the hand and foot skin and soft tissues. We here investigated the effect of the PF127/bleomycin (BLM) hydrogel on the extracellular matrix (ECM) remodeling of skin flaps and the underlying mechanism, thereby providing a new reference point for personalized flap modification and overcoming abrasion resistance- and stability-associated difficulties.</p><p><strong>Methods: </strong>The appropriate PF127/BLM concentration was selected based on the gelation time and drug release curve. Migration assays, scratch assays, and live/dead staining were conducted to verify the effect of PF127/BLM on human skin fibroblasts (HSFs). The effects of PF127/BLM on the ECM were assessed through hematoxylin and eosin and Masson staining. Additionally, we examined the expression of ECM remodeling-related genes and proteins involved in their associated signaling pathway. Finally, the effects of PF127/BLM on organ fibrosis and toxicity to liver and kidney functions were assessed in mice.</p><p><strong>Results: </strong>A 25% PF127/BLM hydrogel was selected as the study concentration. PF127/BLM augmented HSF chemotaxis and proliferation. Furthermore, PF127/BLM promoted subcutaneous ECM remodeling and fibrosis, increased the flap dermis thickness, and reduced the toxic side effects of BLM on liver/lung fibrosis and liver/kidney function. Additional studies confirmed that the PF127/BLM-mediated regulation of ECM remodeling in skin flaps was associated with TGFβ-Col signaling pathway activation.</p><p><strong>Conclusion: </strong>The PF127/BLM hydrogel promoted subcutaneous ECM remodeling and fibrosis, which aided the construction of personalized flaps through the TGFβ-Col signaling pathway, with decreased hepatic, pulmonary, and renal toxicities.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"695-702"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008760","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 prophylactic and therapeutic effects of cannabidiol on lung injury secondary to cardiac ischemia model in rats via PERK/NRF2/CHOP/BCL2 pathway.","authors":"Ozlem Ozmen, Halil Asci, Dincer Uysal, Ilter Ilhan, Rumeysa Taner, Melih Arlıoglu, Adem Milletsever, Serife Tasan","doi":"10.1080/08923973.2024.2384904","DOIUrl":"10.1080/08923973.2024.2384904","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and oxidative stress are key players in lung injury stemming from cardiac ischemia (LISCI). Cannabidiol (CBD) demonstrates tissue-protective properties through its antioxidant, anti-inflammatory, and anti-apoptotic characteristics. This study aims to assess the preventive (p-CBD) and therapeutic (t-CBD) effects of CBD on LISCI.</p><p><strong>Methods: </strong>Forty male Wistar Albino rats were divided into four groups: control (CON), LISCI, p-CBD, and t-CBD. The left anterior descending coronary artery was ligated for 30 min of ischemia followed by 30 min of reperfusion. Lung tissues were then extracted for histopathological, immunohistochemical, genetic, and biochemical analyses.</p><p><strong>Results: </strong>Histopathologically, marked hyperemia, increased septal tissue thickness, and inflammatory cell infiltrations were observed in the lung tissues of the LISCI group. Spectrophotometrically, total oxidant status and oxidative stress index levels were elevated, while total antioxidant status levels were decreased. Immunohistochemically, expressions of cyclooxygenase-1 (COX1), granulocyte colony-stimulating factor (GCSF), interleukin-6 (IL6) were increased. In genetic analyses, PERK and CHOP expressions were increased, whereas Nuclear factor erythroid 2-related factor 2 (NRF2) and B-cell leukemia/lymphoma 2 protein (BCL2) expressions were decreased. These parameters were alleviated by both prophylactic and therapeutic CBD treatment protocols.</p><p><strong>Conclusion: </strong>In LISCI-induced damage, both endoplasmic reticulum and mitochondrial stress, along with oxidative and inflammatory markers, were triggered, resulting in lung cell damage. However, both p-CBD and t-CBD treatments effectively reversed these mechanisms, normalizing all histopathological, biochemical, and PCR parameters.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"594-603"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758480","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":"Anisodamine hydrobromide ameliorates acute lung injury <i>via</i> inhibiting pyroptosis in murine sepsis model.","authors":"Bihua Zhang, Li Luo, Shiqiang Xiong, Yuanyuan Xiao, Ting Zhang, Tao Xiang","doi":"10.1080/08923973.2024.2386331","DOIUrl":"10.1080/08923973.2024.2386331","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of <i>Scopolia tangutica</i> Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered ALI and elucidate the fundamental mechanisms involved.</p><p><strong>Materials and method: </strong>The protective effects of Ani HBr were assessed in two models: <i>in vitro</i>, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and <i>in vivo</i>, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence.</p><p><strong>Results: </strong>Our study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1β in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines.</p><p><strong>Conclusion: </strong>These findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"662-671"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792442","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":"Blocking Gremlin1 inhibits M1 macrophage polarization through Notch1/Hes1 signaling pathway in apical periodontitis.","authors":"Xiao-Yue Guan, Zhi-Chen Wei, Yu-Ting Wang, Wen-Lan Li, Wen-Li Mu, Abdelrahman Seyam, Chen Shi, Tie-Zhou Hou","doi":"10.1080/08923973.2024.2392196","DOIUrl":"10.1080/08923973.2024.2392196","url":null,"abstract":"<p><strong>Background: </strong>Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment.</p><p><strong>Methods: </strong>Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed.</p><p><strong>Results: </strong>Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The <i>in vitro</i> experiments confirmed the above results.</p><p><strong>Conclusion: </strong>Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"703-714"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971041","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":"Sodium hyaluronate and pranoprofen improve visual function and reduce inflammation in patients with dry eye.","authors":"Jian Yin, Zhihang Wu","doi":"10.1080/08923973.2024.2390449","DOIUrl":"10.1080/08923973.2024.2390449","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to investigate the clinical use of sodium hyaluronate (SH) combined with pranoprofen in treating patients with dry eye.</p><p><strong>Methods: </strong>A total of 117 patients with dry eye who were treated in the Traditional Chinese Medicine Hospital of Kunshan from March 2020 and May 2022 were included. According to the therapy approaches, they were treated with SH (SH group), pranoprofen (pranoprofen group), and SH combined with pranoprofen (joint group) (<i>n</i> = 39).</p><p><strong>Results: </strong>The effective rates of dry eye were 79.49%, 74.36% and 94.87% in the SH group, the pranoprofen group and the joint group, respectively (<i>p</i> < 0.05). After treatment, the tear BUT and SIT in the joint group were all prominently increased than those in the other two groups (<i>p</i> < 0.05). The corneal fluorescein staining and dry eye symptom scores in the joint group after treatment were dramatically lower than those in the other two groups (<i>p</i> < 0.001). After treatment, the visual contrast sensitivity (12 c/d, 18 c/d and 24 c/d) in the joint group was markedly higher than those in the other two groups (<i>p</i> < 0.001). The CPR, TNF-α, IFN-γ and IL-1β levels in the joint group were notably decreased than those in other two groups (<i>p</i> < 0.001). After treatment, the VRQOL quality-of-life scores in the joint group were significantly higher than those in the other two groups (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>SH combined with pranoprofen showed clear therapeutic benefit in treating dry eye, and the curative effect was more favorable than with either medication alone.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"627-634"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971042","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":"Selective and effective suppression of pancreatic cancer through MNK inhibition.","authors":"Hui Li, Yang Yao, Rui Hao, Cheng Long","doi":"10.1080/08923973.2024.2391462","DOIUrl":"10.1080/08923973.2024.2391462","url":null,"abstract":"<p><strong>Objective: </strong>The study aimed to explore the role of the Wnt/β-catenin signaling pathway in pancreatic cancer progression and chemoresistance, with a focus on identifying specific factors that distinguish between normal and tumor cells, thereby offering potential therapeutic targets.</p><p><strong>Materials and methods: </strong>We analyzed levels of total and phosphorylated eukaryotic translation initiation factor 4E (eIF4E) and β-catenin in pancreatic cancer and normal pancreatic tissues. Functional assays were used to assess the impact of eIF4E phosphorylation on β-catenin signaling, cell proliferation, and chemoresistance, with MNK kinase involvement determined through gene depletion studies. The MNK kinase inhibitor eFT508 was evaluated for its effects on eIF4E phosphorylation, β-catenin activation, and cell viability in both <i>in vitro</i> and <i>in vivo</i> models of pancreatic cancer.</p><p><strong>Results: </strong>Both total and phosphorylated eIF4E, along with β-catenin, were significantly elevated in pancreatic cancer tissues compared to normal tissues. Phosphorylation of eIF4E at serine 209 was shown to activate β-catenin signaling, enhance cell proliferation, and contribute to chemoresistance in pancreatic cancer. Importantly, these effects were dependent on MNK kinase activity. Depletion of eIF4E reduced cell viability in both pancreatic cancer and normal cells, while depletion of MNK selectively decreased viability in pancreatic cancer cells. Treatment with eFT508 effectively inhibited eIF4E phosphorylation, suppressed β-catenin activation, and reduced pancreatic cancer cell growth and survival <i>in vitro</i> and <i>in vivo</i>, with minimal impact on normal cells.</p><p><p><b>Conclusions:</b> The MNK-eIF4E-β-catenin axis plays a critical role in pancreatic cancer progression and chemoresistance, distinguishing pancreatic cancer cells from normal cells. Targeting MNK kinases with inhibitors like eFT508 presents a promising therapeutic strategy for pancreatic cancer, with potential for selective efficacy and reduced toxicity.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"651-661"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975619","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":"Sunitinib alleviates hepatic ischemia reperfusion injury by inhibiting the JAK2/STAT pathway and promoting the M2 polarization of macrophages.","authors":"Mingxia Li, Juan Tan, Rongsen Zhang, Xiaoxiang Gong, Jun Xie, Cong Liu, Chenhao Wu, Xiaojing Li","doi":"10.1080/08923973.2024.2390455","DOIUrl":"10.1080/08923973.2024.2390455","url":null,"abstract":"<p><strong>Background: </strong>Hepatic ischemia reperfusion injury (IRI) is a common liver surgery complication. This study aims to explore the effect and potential mechanism of Sunitinib - a multi-target tyrosine kinase inhibitor - on hepatic IRI.</p><p><strong>Methods: </strong>We established a hepatic IRI model using C57BL/6 mice, and integrated 40 mg/kg of Sunitinib, solely or combined with 100 μg/kg of coumermycin A1 (C-A1), in the treatment strategy. H&E staining, TUNEL assay, and detection of serum ALT and AST activities were used to assess liver damage. Further, ELISA kits and Western Blots were utilized to determine IL-1β, TNF-α, IL-6, CXCL10, and CXCL2 levels. Primary macrophages, once isolated, were cultured <i>in vitro</i> with either 2 nM of Sunitinib, or Sunitinib in conjunction with 1 μM of C-A1, to gauge their influence on macrophage polarization. qPCR and Western blot were conducted to examine the level of p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2, and M1/M2 polarization markers. To quantify immune cell infiltration, we applied Immunofluorescence.</p><p><strong>Results: </strong>Sunitinib pretreatment significantly alleviated liver injury and reduced p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2 levels. <i>In vitro</i>, Sunitinib treatment curbed M1 polarization induced by LPS + IFN-γ and bolstered M2 polarization triggered by IL-4. C-A1 application upregulated JAK2/STAT pathway phosphorylation and promoted LPS + IFN-γ-induced M1 polarization, which was reversed by Sunitinib treatment. In IL-4-stimulated macrophages, application of C-A1 activated the JAK2/STAT pathway and decreased M2-type macrophages, which was reversed by Sunitinib treatment either.</p><p><strong>Conclusion: </strong>Sunitinib is capable of guiding the polarization of macrophages toward an M2-type phenotype <i>via</i> the inhibition of the JAK2/STAT pathway, thereby exerting a protective effect on hepatic IRI.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"672-684"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999843","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":"Galantamine and wedelolactone combined treatment suppresses LPS-induced NLRP3 inflammasome activation in microglial cells.","authors":"Dilek Saker,Leman Sencar,Gulfidan Coskun,Tugce Sapmaz Ercakalli,Dervis Mansuri Yilmaz,Sait Polat","doi":"10.1080/08923973.2024.2405579","DOIUrl":"https://doi.org/10.1080/08923973.2024.2405579","url":null,"abstract":"CONTEXTInflammasome NLR family pyrin domain-containing 3 (NLRP3) is associated with neurological disorders. Neuroinflammation can be suppressed by inhibiting NLRP3 inflammasome activation, decreasing neurodegenerative disorder progression. We devised a therapeutic technique that can reduce neuroinflammation induced by microglial activation, avoiding neurodegeneration. We aimed to investigate the mechanisms underlying the pharmacological effects of galantamine and wedelolactone by evaluating the response of the nuclear factor kappa B (NF-κB) signaling pathway and NLRP3 inflammasome in lipopolysaccharide (LPS)-activated N9 microglia.METHODSLPS and adenosine triphosphate were used to activate the NLRP3 inflammasome in N9 microglial cells, which were pretreated with galantamine and wedelolactone. Caspase-1, NLRP3, NF-κB, and interleukin (IL)-1β levels were measured using RT-qPCR and immunostaining.RESULTSCombined administration of galantamine and wedelolactone rescued microglial cells from LPS-induced cell death. Furthermore, treatment with galantamine and wedelolactone led to the suppression of NF-κB expression. NLRP3, caspase-1, and IL-1β levels were decreased by the combined treatment.DISCUSSION AND CONCLUSIONThe concurrent administration of galantamine and wedelolactone effectively suppresses the production of inflammatory cytokines and NLRP3 inflammasome activation in microglia. This inhibitory effect is likely linked to the NF-κB signaling pathway modulation. Therefore, this combined treatment is a potential therapeutic approach for neuroinflammatory diseases.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":"38 1","pages":"1-10"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259309","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":"Immunosuppressive effects of triptolide via interleukin-2/receptor signaling.","authors":"Ying Xiong,Yi Yin,Nandani Darshika Kodithuwakku,Jiagang Lv,Juan Wang,Yanxia Ding,Jiao Chen","doi":"10.1080/08923973.2024.2373219","DOIUrl":"https://doi.org/10.1080/08923973.2024.2373219","url":null,"abstract":"BACKGROUNDTriptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression.OBJECTIVEThe present study aimed to explore the potential involvement of IL-2/IL-2R pathway in the immunosuppressive activities of TP.METHODSCultured CTLL-2 cells were utilized to evaluate the potential benefits of TP. Then cell viability was determined by CCK-8 assay, IFN-γ level by ELISA assay, Annexin V-FITC/PI double-staining and CD25 expression by flow cytometry, and protein expression by western blotting. Additionally, rhIL-2-driven lymphocytes following ConA activation were investigated. The interactions of TP with IL-2 and IL-2Rα were investigated by binding assays and molecular dynamics simulations.RESULTSTP treatment attenuated IFN-γ level and cell viability in both rhIL-2-induced CTLL-2 cells and rhIL-2-driven splenic lymphocytes. TP treatment increased cellular apoptosis/necrosis and cleaved PARP-1 level, while suppressed c-Myc level in rhIL-2-induced CTLL-2 cells. Additionally, TP treatment reduced CD25 expression on CTLL-2 cell surface. Notably, the phosphorylation protein levels in IL-2R signaling pathways were inhibited by TP exposure prior to rhIL-2 stimulation. SPR and BLI assays verified TP that directly bound to rhIL-2 and rmIL-2Rα, respectively. Molecular simulations suggested that TP bound at the interface of IL-2 and IL-2Rα near the hydrophobic patch composed of F62, L92 on IL-2 and L23, I46, V139 on IL-2Rα, resulting in decreased binding free energy between IL-2 and IL-2Rα.CONCLUSIONSThese findings collectively emphasized that TP interfered IL-2/IL-2Rα interactions, down-regulated IL-2Rα expression, and inhibited IL-2R signaling pathways activation, thereby leading to the immune cells being desensitized to rhIL-2 and exhibiting immunosuppressive properties.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":"25 1","pages":"1-14"},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259307","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":"Anti-inflammatory effect of proanthocyanidins from blueberry through NF-κβ/NLRP3 signaling pathway <i>in vivo</i> and <i>in vitro</i>.","authors":"Xinyao Liu, Lulu Zang, Jiabao Yu, Jinjin Yu, Siqi Wang, Lili Zhou, Huixin Song, Yajing Ma, Xiaofeng Niu, Weifeng Li","doi":"10.1080/08923973.2024.2358770","DOIUrl":"10.1080/08923973.2024.2358770","url":null,"abstract":"<p><strong>Background: </strong>Systemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC.</p><p><strong>Methods: </strong>Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model <i>in vitro</i>, while endotoxin shock mouse models were constructed by LPS <i>in vivo</i>. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis.</p><p><strong>Results: </strong>Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway.</p><p><strong>Conclusion: </strong>PC might have the potential ability of anti-inflammatory effects <i>via</i> modulation of the NF-κB/NLRP3 signaling pathway.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"425-435"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075950","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}