Immunopharmacology and Immunotoxicology最新文献

{"title":"Macrophages morphology and cytokine reeducation by <i>ex situ</i> copper thiol complexes.","authors":"Jorge Xool-Tamayo, Víctor Ermilo Arana-Argaez, Fabiola Villa-de la Torre, Ivan Chan-Zapata, Rossana F Vargas-Coronado, Juan V Cauich-Rodríguez","doi":"10.1080/08923973.2023.2245559","DOIUrl":"10.1080/08923973.2023.2245559","url":null,"abstract":"<p><strong>Objective: </strong>To study the reeducation effect of copper thiol complexes on macrophage morphology and cytokine expression.</p><p><strong>Methods: </strong>The effect of copper thiol complexes was assessed on murine macrophages by the cell morphology observed through optical microscopy, while the expression of cytokines by protein abundance after stimulation. A viability experiment was performed on PMBC to confirm that copper complexes do not affect other cells.</p><p><strong>Results: </strong>The M1 shape was reported after treatment with copper thiol complexes at 1-200 µM, while M2 behavior was documented between 50 and 800 µM. Surprisingly, a thin elongate morphology was observed between 400-800 µM like the M2 shape. The expression of M1 cytokines was noted ranging from 1 to 100 µM, with the highest yield at 1 µM (2243 pg/µL) for the copper-penicillamine complex. M2 production behavior was observed at 1-800 µM, with the highest abundance close to 1150 pg/µL (200-400 µM) was quantified from the copper-cysteine complex. Finally, LCCu complexes did not induce a cytotoxic response on PBMC while exhibiting a high IL-4 and IL-10 production, similar to their gold analogs.</p><p><strong>Conclusions: </strong>The capacity of copper thiol complexes to reeducate M1 to M2 morphoexpression can be promising for cell protection by using copper thiol penicillamine or immuno-regeneration of tissues when using copper thiol cysteine.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997774","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":"Effects of erucin on inflammatory mediators and antioxidant enzymes' expression in TNF-α-stimulated human oral epithelial cells.","authors":"Masahiro Shimoyama, Yoshitaka Hosokawa, Ikuko Hosokawa, Kazumi Ozaki, Keiichi Hosaka","doi":"10.1080/08923973.2023.2250551","DOIUrl":"10.1080/08923973.2023.2250551","url":null,"abstract":"<p><strong>Objectives: </strong>Periodontitis is a chronic inflammatory disease induced by periodontal disease-causing bacteria. It has been shown that excessive immune response against bacteria is involved in periodontal tissue destruction including alveolar bone resorption. Erucin is a biologically active substance found in cruciferous plants such as arugula and is classified as an isothiocyanate. No previous studies have attempted to use erucin in the treatment of periodontitis, and there are no papers that have examined the effects of erucin on periodontal resident cells. The purpose of this study was to analyze the effects of erucin on the production of inflammatory and antioxidant mediators produced by tumor necrosis factor (TNF)-α-stimulated TR146 cells, an oral epithelial cell line, including its effects on signaling molecules.</p><p><strong>Methods: </strong>Cytokine and chemokine levels were measured by ELISA. Protein expression in TR146 cells and activations of signal transduction pathway were determined by Western blotting.</p><p><strong>Results: </strong>Our results indicate that erucin suppresses interleukin-6 and CXC-chemokine ligand 10 production and vascular cell adhesion molecule-1 expression in TNF-α-stimulated TR146 cells. In addition, erucin induced the production of the antioxidant enzymes, Heme Oxygenase-1 and NAD(P)H quinone dehydrogenase 1 in TR146 cells. Furthermore, erucin suppressed TNF-α-stimulated nuclear factor-κB, signal transducer and activator of transcription3, and phospho-70S6 Kinase-S6 ribosomal protein signaling pathways in TR146 cells. We have shown that erucin has anti-inflammatory effects on oral epithelial cells and also induces the production of antioxidant mediators.</p><p><strong>Conclusions: </strong>These results suggest that erucin may provide a new anti-inflammatory agent that can be used in the treatment of periodontitis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10104710","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":"Hydroxychloroquine exacerbates imiquimod-induced psoriasis-like dermatitis through stimulating overexpression of IL-6 in keratinocytes.","authors":"Ling-Jung Yen, Ying-Chin Chen, Kai-Chun Wang, Meng-Chieh Shih, Chia-Ling Li, Sheng-Jie Yu, Ling-Ying Lu","doi":"10.1080/08923973.2023.2281283","DOIUrl":"10.1080/08923973.2023.2281283","url":null,"abstract":"<p><strong>Objective: </strong>Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model.</p><p><strong>Methods: </strong>Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ). Besides control, all were topically treated with IMQ for 5 days. Pharmacological effects and mechanisms of HCQ were assessed by clinical severity of dermatitis, histopathology, and flow cytometry. HaCaT cells were co-treated with both HCQ and recombinant IL-17A, followed by the detection of proinflammatory cytokine expression and gene profiles through enzyme-linked immunosorbent assay and next-generation sequencing.</p><p><strong>Results: </strong>In the pre-treated and co-treated HCQ groups, skin redness and scaling were significantly increased compared to the IMQ-Only group, and Th17 cell expression was also upregulated. Acanthosis and CD11b⁺IL23⁺ dendritic cell (DC) infiltration were observed in the HCQ treatment group. IL-6 overexpression was detected in both the HaCaT cells and skin from the experimental mice. Psoriasis-related genes were regulated after being co-treated with HCQ and recombinant IL-17A in HaCaT cells.</p><p><strong>Conclusions: </strong>HCQ exacerbates psoriasis-like skin inflammation by increasing the expression of IL-6, stimulating DC infiltration, and promoting Th17 expression in the microenvironment of the skin.</p><p><strong>Key messages: </strong>This study provided possible mechanisms for inducing psoriasis during HCQ treatment through an animal model.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498313","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":"Leptin/lipopolysaccharide-treated dendritic cell vaccine improved cellular immune responses in an animal model of breast cancer.","authors":"Pedram Basirjafar, Raziyeh Zandvakili, Javad Masoumi, Nahid Zainodini, Zahra Taghipour, Hossein Khorramdelazad, Soheila Yousefi, Tayyebeh Tavakoli, Mahboobeh Vatanparast, Sepehr Safdel, Mahsa Gheitasi, Fatemeh Ayoobi, Bahar Naseri, Abdollah Jafarzadeh","doi":"10.1080/08923973.2023.2253989","DOIUrl":"10.1080/08923973.2023.2253989","url":null,"abstract":"<p><strong>Purpose: </strong>In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers.</p><p><strong>Materials and methods: </strong>Tumors were established in mice by subcutaneously injecting 7 × 10⁵ 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-β) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively.</p><p><strong>Results: </strong>Leptin/LPS-treated mDC group was more efficient in blunting tumor growth (<i>p</i> = .0002), increasing survival rate (<i>p</i> = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs (<i>p</i> < .001) and TH1 cells (<i>p</i> < .01); promoted the production of IFN-γ (<i>p</i> < .0001) and IL-12 (<i>p</i> < .001) by splenocytes; enhanced the T-bet (<i>p</i> < .05) and Granzyme B (<i>p</i> < .001) expression, whereas decreased the TGF-β and FOXP3 expression (<i>p</i> < .05).</p><p><strong>Conclusion: </strong>Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10494093","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 pregabalin on renal and renal endothelial damage in sepsis induced by lipopolysaccharide.","authors":"Dilek Çevik, Nurhan Gümral, Rahime Aslankoç, Özlem Özmen, Arzu Yalçın, Oğuzhan Kavrık","doi":"10.1080/08923973.2023.2250911","DOIUrl":"10.1080/08923973.2023.2250911","url":null,"abstract":"<p><strong>Objective: </strong>We investigated the protective effects of pregabalin (PRG) on kidney and renal endothelial damage in sepsis induced by Lipopolysaccharide (LPS).</p><p><strong>Materials and methods: </strong>Rats were randomly divided into three groups as control, LPS and LPS+PRG. Saline solution was administered 30 mg/kg orally and 5 mg/kg intraperitoneally (i.p.) to the control group. LPS was applied as 5 mg/kg, i.p. to the LPS group. In the LPS+PRG group, PRG at 30 mg/kg orally and one hour before LPS administration, one hour later 5 mg/kg i.p. LPS was applied. Rats were sacrificed 6 hours after LPS administration.</p><p><strong>Results: </strong>White Blood Cell (WBC), granulocyte, Blood Urea Nitrogen (BUN), creatinine, uric asid, Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) significantly increased (<i>p</i><0.05); platelets (PLT), activated partial thromboplastin time (aPTT) and Total Antioxidant Status (TAS) significantly decreased in the LPS group compared to the control group (<i>p</i><0.05). In the LPS+PRG group WBC, granulocyte, BUN, creatinine, uric asid, TOS and OSI significantly decreased (<i>p</i><0.05); PLT, aPTT and TAS significantly increased compared to the LPS group(<i>p</i><0.05). Histopathological examinations showed that kidney and renal endothelial damage in the LPS group decreased in the LPS+PRG group. Immunohistochemically IL1-β, IL-6, IL-10, TNF-α expressions in kidney tissue and Toll-Like Receptors-4 (TLR-4) and NF-κB expressions in the renal endothelial tissue significantly increased in the LPS group compared to the control group and significantly decreased in the LPS+PRG group compared to the LPS group (<i>p</i><0.001).</p><p><strong>Conclusions: </strong>Sepsis causes kidney and renal endothelial damage and PRG reduces this damage. Therefore PRG can be used in prophylactic treatment in sepsis, supported by more studies.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160428","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":"Expression of calcitonin gene-related peptide in atopic dermatitis and correlation with distress.","authors":"Saly Abdelhadi, Klas Nordlind, Björn Johansson, Elvar Theodorsson, Mikael Holst, Louise Lönndahl","doi":"10.1080/08923973.2023.2253988","DOIUrl":"10.1080/08923973.2023.2253988","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD.</p><p><strong>Methods: </strong>Twenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique.</p><p><strong>Results: </strong>The total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis.</p><p><strong>Conclusions: </strong>CGRP may have a role in both the inflammatory process and distress, in AD.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10542736","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":"Gigantol protects retinal pigment epithelial cells against high glucose-induced apoptosis, oxidative stress and inflammation by inhibiting MTDH-mediated NF-kB signaling pathway.","authors":"You Chen, Tong Zhao, Mengyu Han, Yi Chen","doi":"10.1080/08923973.2023.2247545","DOIUrl":"10.1080/08923973.2023.2247545","url":null,"abstract":"<p><strong>Objective: </strong>As a frequent complication of diabetes mellitus (DM), diabetic retinopathy (DR) is now one of the major causes of blindness. Recent reports have shown that retinal pigment epithelial cell (RPEC) damage plays an essential part in DR development and progression. This work intended to explore the potential effects of Gigantol on high glucose (HG)-stimulated RPEC damage and identify potential mechanisms.</p><p><strong>Methods: </strong>Cell viability, cell damage, and cell apoptosis were evaluated by CCK-8, lactate dehydrogenase (LDH) and flow cytometry assays. The levels of oxidative stress biomarkers and pro-inflammatory cytokines were assessed using corresponding commercial kits and ELISA. Additionally, the levels of MTDH and NF-kB signaling pathway-related proteins were detected by western blotting.</p><p><strong>Results: </strong>Gigantol dose-dependently enhanced cell viability and decreased apoptosis in HG-challenged ARPE-19 cells. Also, Gigantol notably relieved oxidative stress and inflammatory responses in ARPE-19 cells under HG conditions. Gigantol dose-dependently suppressed MTDH expression. In addition, MTDH restoration partially counteracted the protective effects of Gigantol on ARPE-19 cells subject to HG treatment. Mechanically, Gigantol inactivated the NF-kB signaling pathway, which was partly restored after MTDH overexpression.</p><p><strong>Conclusion: </strong>Our findings suggested that Gigantol protected against HG-induced RPEC damage by inactivating the NF-kB signaling via MTDH inhibition, offering a potent therapeutic drug for DR treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186152","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":"Cynarin ameliorates dextran sulfate sodium-induced acute colitis in mice through the STAT3/NF-κB pathway.","authors":"Shumin Chen, Shaoshuai Tang, Chunbin Zhang, Yuanyue Li","doi":"10.1080/08923973.2023.2281281","DOIUrl":"10.1080/08923973.2023.2281281","url":null,"abstract":"<p><strong>Objective: </strong>Cynarin is a derivative of hydroxycinnamic acid presented in various medicinal plants, such as <i>Cynara scolymus</i> L. and <i>Onopordum illyricum</i> L. To date, the antioxidant and antihypertensive activities of cynarin have been reported. However, whether cynarin has a therapeutic impact on ulcerative colitis (UC) is unclear. Therefore, the aim of this study was to explore the potential effect of cynarin on dextran sulfate sodium (DSS)-induced acute colitis <i>in vivo</i> and on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced RAW264.7 and J774A.1 cellular inflammation model <i>in vitro</i>.</p><p><strong>Methods and results: </strong>In this study, we investigated that cynarin alleviated clinical symptoms in animal models, including disease activity index (DAI) and histological damage. Furthermore, cynarin can attenuate colon inflammation through decreasing the proportion of neutrophils in peripheral blood, reducing the infiltration of neutrophils, and macrophages in colon tissue, inhibiting the release of pro-inflammatory cytokines and suppressing the expression of STAT3 and p65. In cellular inflammation models, cynarin inhibited the expression of M1 macrophage markers, such as TNF-α, IL-1β, and iNOS. Besides, cynarin suppressed the expression of STAT3 and p65 as well as the phosphorylation of STAT3, p65. Cynarin inhibited the polarization of RAW264.7 and J774A.1 cells toward M1 and alleviated LPS/IFN-γ-induced cellular inflammation.</p><p><strong>Conclusion: </strong>Considering these results, we conclude that cynarin mitigates experimental UC partially through inhibiting the STAT3/NF-кB signaling pathways and macrophage polarization toward M1. Accordingly, cynarin might be a potential and effective therapy for UC.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481099","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":"Celecoxib Alleviates the DSS-induced ulcerative colitis in mice by enhancing intestinal barrier function, inhibiting ferroptosis and suppressing apoptosis","authors":"Yaxian Li, Mengdi Ma, Xiaodong Wang, Jing Li, Ziqing Fang, Jianhui Li, Bo Yang, Yida Lu, Xin Xu, Yongxiang Li","doi":"10.1080/08923973.2023.2300508","DOIUrl":"https://doi.org/10.1080/08923973.2023.2300508","url":null,"abstract":"Introduction: Ulcerative colitis (UC) is an inflammatory intestine disease characterized by dysfunction of the intestinal mucosal barrier, ferroptosis, and apoptosis. Previous researches suggest th...","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139067400","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":"Secreted phosphoprotein 1 regulates natural compound 3',4',5,7-tetrahydroxyflavone to inhibit mast cell-mediated allergic inflammation.","authors":"Shiling Hu, Jue Wang, Haoyun Bai, Chaohua Feng, Zhenqi Zhou, Zhuoyin Xue, Wen Zhang, Yongjing Zhang, Nan Wang, Langchong He","doi":"10.1080/08923973.2023.2228478","DOIUrl":"10.1080/08923973.2023.2228478","url":null,"abstract":"<p><strong>Background: </strong>Mast cells (MCs) are important effector cells in anaphylaxis and anaphylactic disease. 3',4',5,7-tetrahydroxyflavone (THF) presents in many medicinal plants and exerts a variety of pharmacological effects. In this study, we evaluated the effect of THF on C48/80-induced anaphylaxis and the mechanisms underlying its effects, including the role of secreted phosphoprotein 1 (SPP1), which has not been reported to IgE-independent MC activation.</p><p><strong>Results: </strong>THF inhibited C48/80-induced Ca²⁺ flow and degranulation <i>via</i> the PLCγ/PKC/IP3 pathway <i>in vitro</i>. RNA-seq showed that THF inhibited the expression of SPP1 and downstream molecules. SPP1 is involved in pseudo-anaphylaxis reactions. Silencing SPP1 affects the phosphorylation of AKT and P38. THF suppressed C48/80-induced paw edema, hypothermia and serum histamine, and chemokines release <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Our results validated SPP1 is involved in IgE-independent MC activation anaphylactoid reactions. THF inhibited C48/80-mediated anaphylactoid reactions both <i>in vivo</i> and <i>in vitro</i>, suppressed calcium mobilization and inhibited SPP1-related pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9734793","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}