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":"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":"Crocin as a potential therapeutic agent for multiple sclerosis: insights from experimental autoimmune encephalomyelitis model in mice.","authors":"Alireza Pazoki, Mahbobeh Askaripour, Simin Zargarani, Esmaeil Yazdanpanah, Dariush Haghmorad","doi":"10.1080/08923973.2024.2445747","DOIUrl":"https://doi.org/10.1080/08923973.2024.2445747","url":null,"abstract":"<p><strong>Objective: </strong>Multiple sclerosis (MS) is a prevalent autoimmune disorder characterized by neuroinflammation and demyelination in the central nervous system (CNS), leading to neurological dysfunction. Despite advances in treatment, there remains an unmet need for safe and effective therapies. Crocin, a bioactive constituent of saffron, has demonstrated anti-inflammatory and immunoregulatory properties in various disease models. This study investigates the therapeutic potential of Crocin in a murine model of MS, experimental autoimmune encephalomyelitis (EAE).</p><p><strong>Methods and results: </strong>Female C57BL/6 mice were induced with EAE and treated with different doses of Crocin. Clinical severity, CNS pathology, T cell proliferation, cytokine production, and transcription factor expression were assessed. Crocin-treated mice showed reduced clinical severity, inflammation, and demyelination in the CNS compared to controls. Moreover, Crocin attenuated T cell proliferation and modulated cytokine production, promoting an anti-inflammatory cytokine profile while suppressing pro-inflammatory cytokines. Additionally, Crocin altered the expression of transcription factors associated with T cell differentiation, favoring regulatory T cell responses.</p><p><strong>Discussion: </strong>These findings suggest that Crocin exerts therapeutic effects in EAE by modulating neuroinflammation and immune responses. Further studies are warranted to elucidate the mechanisms underlying Crocin's immunomodulatory properties and its potential as a treatment for MS.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893939","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":"Pesticide exposure promotes disease activity by decreasing lymphoproliferative activity and increasing IL-4 production in systemic sclerosis patients.","authors":"Ahmad Alsulimani, Shukla Das, Naseem Akhter, Abrar Ahmad, Arshad Jawed, Saba Beigh, Mazin A Zamzami, Salwa Al-Thawadi, Mohamed Yahya Alfoud, Basu Dev Banerjee, Sajad Ahmad Dar","doi":"10.1080/08923973.2024.2445731","DOIUrl":"https://doi.org/10.1080/08923973.2024.2445731","url":null,"abstract":"<p><strong>Background: </strong>One of the common findings in systemic sclerosis (SSc) patients has been long-term exposure to environmental toxins such as pesticides. However, the data available shows an equivocal association between pesticide exposure and autoimmunity in SSc.</p><p><strong>Methods: </strong>We investigated the levels of organochlorine pesticides (OCPs) in blood of 20 SSc patients and 17 healthy controls, and also studied their effect <i>in-vitro</i> on T lymphocytes and their functional responses.</p><p><strong>Results: </strong>We found higher levels of hexachlorocyclohexane (HCH- α-, β-, and γ) and o,p'-dichlorodiphenyltrichloroethane (DDT) metabolite (p,p΄-DDE) in blood of SSc patients. <i>In vitro</i> treatment of SSc patient PBMCs with either of HCH (100 mM) or DDT (50 µM) caused a significant increase merely in CD8⁺ memory (CD8⁺CD45RO⁺) T lymphocytes. We also observed reduced FoxP3 expression in CD4⁺CD25⁺ (regulatory T cells) of SSc patients. Neither HCH nor DDT exposure of SSc PBMCs altered significantly the secretion of IL-2, IL-10, or IFN-γ, but both of these pesticides elevated their IL-4 (a pro-fibrotic cytokine) secretion.</p><p><strong>Conclusion: </strong>Taken together, our findings indicate that persistent exposure to these OCPs results in decreased lymphoproliferative activity which promotes disease activity by producing pro-fibrotic cytokine(s). Thus, SSc patients are less able to initiate or augment an immune response to foreign antigens, when there is substantial suppression of lymphocyte function, which increases their susceptibility to infection. Strategies to prevent and control pesticide exposure may play an important role in reducing the morbidity and mortality associated with this disease.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893959","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":"Matairesinol repolarizes M2 macrophages to M1 phenotype to induce apoptosis in triple-negative breast cancer cells.","authors":"Amol Chaudhary, Prajakta Patil, Prerna Raina, Ruchika Kaul-Ghanekar","doi":"10.1080/08923973.2024.2425028","DOIUrl":"https://doi.org/10.1080/08923973.2024.2425028","url":null,"abstract":"<p><strong>Objective: </strong>Triple-Negative Breast Cancer (TNBC), the most challenging subtype of Breast Cancer (BC), currently lacks targeted therapy, presenting a significant therapeutic gap in its management. Tumor Associated Macrophages (TAMs) play a significant role in TNBC progression and could be targeted by repolarizing them from M2 to M1 phenotype. Matairesinol (MAT), a plant lignan, has been shown to exhibit anticancer, anti-inflammatory and immunomodulatory activities. In this study, we explored how MAT-induced repolarization of THP-1-derived M2 macrophages towards the M1 phenotype, which could effectively target the TNBC cell line, MDA-MB-231.</p><p><strong>Methods: </strong>The differential expression of genes in THP-1-derived macrophages at mRNA levels was evaluated by RNAseq assay. An inverted microscope equipped with a CMOS camera was utilized to capture the morphological variations in THP-1 cells and THP-1-derived macrophages. Relative mRNA expression of M1 and M2 specific marker genes was quantified by qRT-PCR. Cell viability and induction of apoptosis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1 dye) assays, respectively.</p><p><strong>Results: </strong>MAT reduced the viability of M2a and M2d macrophages and repolarized them to M1 phenotype. Conditioned medium (CM) from MAT-treated M2a and M2d macrophages significantly reduced the viability of TNBC cells by apoptosis.</p><p><strong>Conclusion: </strong>Targeting M2 macrophages is an important strategy to regulate cancer progression. Our study provides evidence that MAT may be a promising drug candidate for developing novel anti-TNBC therapy. However, further studies are warranted to thoroughly elucidate the molecular mechanism of action of MAT and evaluate its therapeutic potential in TNBC <i>in vitro</i> and <i>in vivo</i> models.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893949","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":"<i>Cannabis sativa</i> alleviates experimentally acetic acid- induced ulcerative colitis in rats: targeting CB1/SIRT/MAPK signaling pathways.","authors":"Rania Elgohary, Enayat A Omara, Abeer Salama","doi":"10.1080/08923973.2024.2445733","DOIUrl":"https://doi.org/10.1080/08923973.2024.2445733","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a frequent inflammatory bowel disease (IBD) that causes long-lasting inflammation in the innermost lining of the rectum and colon.</p><p><strong>Objective: </strong>The aim of this study was to evaluate the therapeutic effect of <i>Cannabis sativa</i> (<i>C. sativa</i>) on the amelioration of acetic acid-induced colitis in rats.</p><p><strong>Materials and methods: </strong>Group 1: normal control group was intrarectally administered saline solution (0.9%); group 2: acetic acid (AA) group was given AA intra-rectally (2 mL of 4% (v/v) in 0.9% NaCl) once.; group 3&4: This group represented the ulcerative colitis-induced rats that were injected with acetic acid intra-rectally, then s.c. injection with <i>C. sativa</i> (20 and 40 mg/kg daily for 8 days).</p><p><strong>Results: </strong>Colonic architectural abnormality significantly improved after pretreatment with <i>C. sativa</i>. Additionally, it significantly reduced the MDA level and prevented the depletion of GSH content. Moreover, <i>C. sativa</i> administration showed suppressive activities on pro-inflammatory cytokines, including NF-κB, MAPK, ERK, PI3K, AKT, HIF-1α, and TLR4. Moreover, it significantly upregulated the level of SIRT and CB1 in the colon tissue.</p><p><strong>Conclusion: </strong>This study provided a novel impact for CB1 receptor activation produced by <i>C. sativa</i> against AA-induced UC in rats through inhibiting the TLR-4 MAPK/ERK, PI3K, and NFκB signaling pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894038","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":"Role of myeloid-derived suppressor and Th17/Treg cells in post-COVID-19 Rhino-Orbital mucormycosis cases.","authors":"Praveen Kumar Singh, Gargi Rai, Shukla Das, Mohammad Ahmad Ansari, Rnda I Ashgar, Neelima Gupta, Vipin Arora, Sonal Sharma, Sajad Ahmad Dar","doi":"10.1080/08923973.2024.2437482","DOIUrl":"https://doi.org/10.1080/08923973.2024.2437482","url":null,"abstract":"<p><p><b>Background:</b> Rhino-Orbital-Cerebral Mucormycosis (ROCM) cases increased sharply in India during the second COVID-19 wave. Due to uncontrolled hyperglycemia, prolonged steroid use, and high ferritin levels, the immune system was dysregulated throughout this surge.</p><p><p><b>Methods:</b> Our study examined post-COVID-19 ROCM patients' T regulatory cell (Treg), T helper 17 cell (Th17) and Myeloid derived suppressor cell (MDSC) levels before and after three months of treatment. T cell activation and MDSC profile were measured in peripheral blood from 20 post-COVID-19 mucormycosis patients and 20 age-matched controls.</p><p><p><b>Results:</b> Compared to controls, cases had significantly greater Th17 cells (CD4⁺IL-23R⁺) before and after treatment (<i>p</i> < 0.05), with no significant change between pre- and post-treatment. In pretreatment cases, Treg cells (CD4⁺CD25⁺FoxP3⁺) were lower than controls, but dramatically increased (<i>p</i> < 0.05) following treatment. Further, these patients had significantly higher rates of monocytic (m) MDSCs (CD14⁺HLA-DR^low/-) compared to healthy persons (<i>p</i> < 0.05). Interestingly, after three months of treatment, mMDSC levels dropped to levels similar to healthy controls. Similarly, ROCM patients had higher levels of granulocytic (g) MDSCs (HLA-DR^low/-CD33⁺CD11b⁺CD66⁺) than healthy controls, although these levels normalized after three months. Patients had considerably greater expression levels of RORγt, TGF-β, and IL-10 mRNA before therapy compared to healthy controls. FoxP3 and Arg-1 mRNA expression was lower in pretreatment patients than in healthy people. After treatment, these individuals' IL-10, FoxP3, and Arg-1 mRNA expression increased.</p><p><p><b>Conclusion:</b> MDSCs may play a role in mucormycosis immunological dysregulation, suggesting that restoring balance may improve patient outcomes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854021","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":"Combined bisoprolol and trimetazidine ameliorate arsenic trioxide -induced acute myocardial injury in rats: targeting PI3K/GSK-3β/Nrf2/HO-1 and NF-κB/iNOS signaling pathways, inflammatory mediators and apoptosis.","authors":"Yasmin M Ahmed, Ehab A M El-Shoura, Magy R Kozman, Basel A Abdel-Wahab, Asmaa Ramadan Abdel-Sattar","doi":"10.1080/08923973.2024.2435323","DOIUrl":"10.1080/08923973.2024.2435323","url":null,"abstract":"<p><strong>Background: </strong>Arsenic-trioxide (ATO) is an effective therapy for acute promyelocytic leukemia. Unfortunately, its utility is hindered by the risk of myocardial injury. Both bisoprolol (BIS) and trimetazidine (TMZ) have various pharmacological features, including anti-oxidant, anti-inflammatory, and anti-apoptotic properties.</p><p><strong>Aim: </strong>The cardioprotective effects of BIS and TMZ were studied, and their mechanistic role in ameliorating ATO-induced myocardial injury.</p><p><strong>Materials and methods: </strong>Forty male Wistar rats were randomly allotted into five groups as follows: normal control group (received normal saline, orally), ATO group (7.5 mg/kg, orally), BIS (8 mg/kg, orally), TMZ (60 mg/kg, orally), and finally combination group (BIS+TMZ+ATO). Following 21 days, samples of serum and cardiac tissues were obtained to perform biochemical, molecular, and histopathological investigations.</p><p><strong>Results: </strong>The present study showed that ATO caused myocardial injury evidenced by changes in serum biomarkers (Aspatate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase-MB, and cardiac troponin-1), electrolyte imbalance, and lipid profiles alongside histopathologic changes. In addition, ATO administration significantly elevated malondialdehyde, nicotinamide adenine dinucleotide phosphate hydrogen oxidase, myloperoxidase, total nitrite, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, interleukin-6, 8-Hydroxy-2'-deoxyguanosine, nuclear factor NF-kappa-B p65 subunit, glycogen synthase kinase-3 beta, and caspase-3 expression contemporaneously with down-regulation of reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, heme oxygenase 1, nuclear factor erythroid 2-related factor 2, phosphatidylinositol-3 kinase, p-PI3K, and Bcl-2 expression. Interestingly, pretreatment with BIS and TMZ significantly reversed the detrimental effects of ATO-induced myocardial injury at both cellular and molecular levels. Otherwise, combining the two drugs displayed more enhancement than each drug alone.</p><p><strong>Conclusion: </strong>The present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739259","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":"1,25(OH)₂D₃-treated mouse bone marrow-derived dendritic cells alleviate autoimmune hepatitis in mice by improving TFR/TFH imbalance.","authors":"Juan Dai, Jianguo Song, Xueping Chen, Fei Ding, Yanbo Ding, Liang Ma, Liwen Zhang","doi":"10.1080/08923973.2024.2435314","DOIUrl":"10.1080/08923973.2024.2435314","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune hepatitis (AIH) is a chronic progressive autoimmune disease with unclear etiology. As a bioactive metabolite of Vitamin D, 1,25(OH)₂D₃ can stimulate the production of tolerogenic dendritic cells (DCs) that overexpress programmed cell death ligand 1 (PD-L1). Although these cells have been shown to play a part in autoimmune diseases, their role in AIH remains unclear.</p><p><strong>Methods: </strong>This study aimed to investigate the potential effect of 1,25(OH)₂D₃-modulated DCs (PD-L1^high VD3-DCs) in a murine model of experimental autoimmune hepatitis (EAH).</p><p><strong>Results: </strong>Our results showed that intravenous injection of PD-L1^high VD3-DCs significantly attenuated liver injury and EAH severity in mice. In addition, PD-L1^high VD3-DC infusion improved the imbalance between splenic regulatory T cells (TFR) and follicular helper T (TFH) cells in EAH mice by increasing the number of TFR cells and restoring TFR/TFH ratio. Also, PD-L1^high VD3-DC infusion selectively promoted TFR expansion and inhibited TFH differentiation. Furthermore, PD-L1^high VD3-DC infusion increased TGF-β and IL-10 production, inhibited IL-21 secretion, upregulated key TFH transcriptional factors, and reduced the levels of serum immunoglobulins in EAH mice.</p><p><strong>Conclusions: </strong>To sum up, PD-L1^high VD3-DC infusion could control EAH progression in mice by regulating TFR/TFH imbalance, indicating PD-L1^high VD3-DC infusion might be a promising therapeutic approach for AIH treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739255","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":"Effect of atorvastatin on lipopolysaccharide-induced lung inflammation and hypoxia in mice; modulation of HIF-1α, CINC and MIP-2.","authors":"Abeer Salama, Amany A El-Fadaly, Rania Elgohary","doi":"10.1080/08923973.2024.2436089","DOIUrl":"https://doi.org/10.1080/08923973.2024.2436089","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury is a crucial pathological state, particularly in some severe infectious respiratory illnesses, distinguished by acute inflammation, pulmonary edema, hypoxia, and neutrophil recruitment. Cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) play a vital role in neutrophil recruitment.</p><p><strong>Objective: </strong>Here, we validated the potential repressing effect of atorvastatin on acute lung injury induced by lipopolysaccharide (LPS) in mice.</p><p><strong>Materials and methods: </strong>Mice were injected with LPS (250 μg/kg; i.p.) daily for 7 days, and atorvastatin (25 and 50 mg/kg; orally) daily along with LPS.</p><p><strong>Results: </strong>Atorvastatin ameliorated oxidative stress as evidenced by increased reduced glutathione (GSH) and nuclear factor-erythroid 2 related factor 2 (Nrf2) levels and decreased malondialdehyde (MDA) levels. Additionally, it lessened inflammatory biomarkers including tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), CINC, and MIP-2, as well as hypoxia biomarker hypoxia-inducible factor-1α (HIF-1α). Moreover, atorvastatin slowed the progression of lung tissue histological lesions.</p><p><strong>Conclusion: </strong>Collectively, the present study suggests that, atorvastatin effectively protects against LPS-induced acute lung injury through inhibition of oxidative stress, inflammation, hypoxia, and neutrophil recruitment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780134","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}