{"title":"Innovative Approaches to Psoriasis: Small Molecules Targeting Key Signaling Pathways.","authors":"Meeral Gosia, Gaurav Doshi, Siddhi Bagwe Parab, Angel Godad","doi":"10.1080/08820139.2025.2449960","DOIUrl":"https://doi.org/10.1080/08820139.2025.2449960","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis (Pso) is a chronic, immune-mediated dermatological condition characterized by dysregulated inflammatory responses and the hyperproliferation of keratinocytes. Biologics, which target specific cytokines such as IL-17 and IL-23, have revolutionized the management by addressing key drivers of its pathophysiology. Despite their efficacy, biologics are not without limitations, including the need for intermittent administration and ongoing monitoring. In contrast, small molecules offer a promising alternative by selectively inhibiting key signaling pathways that modulate pro-inflammatory cytokines involved in the inflammatory cascade.</p><p><strong>Methods and results: </strong>This review suggests a new therapeutic strategy for Pso treatment, emphasizing the intricate relationships between small molecules and important signaling pathways involved in the pathophysiology of skin conditions. Improving treatment outcomes and reducing the side effects associated with conventional medicines, this review aims to better understand how tailored small-molecule inhibitors might efficiently control these pathways. This creative approach promotes the creation of individualized treatment plans that can greatly enhance the quality of life of patients with Psoby utilizing the knowledge gathered from recent developments in signaling pathway research.</p><p><strong>Conclusion: </strong>This review delves into the molecular mechanisms underlying Pso and explores how small molecules can be harnessed to enhance treatment outcomes, presenting a new paradigm for managing this chronic skin disorder.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-37"},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004837","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}
Lijie Wang, Jiabo Yuan, Ruiqi Zhao, Congyao Wang, Zhuying Li
{"title":"Timosaponin A-III Alleviates Asthma-Induced Airway Inflammation, Th17 Cell Differentiation, and STAT3/RORγt Pathway.","authors":"Lijie Wang, Jiabo Yuan, Ruiqi Zhao, Congyao Wang, Zhuying Li","doi":"10.1080/08820139.2025.2450239","DOIUrl":"https://doi.org/10.1080/08820139.2025.2450239","url":null,"abstract":"<p><strong>Introduction: </strong>T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway.</p><p><strong>Methods: </strong> Ovalbumin (OVA)-induced asthma murine models were developed, and TA3 (10 or 20 mg/kg) was gavage daily during OVA challenge. Murine naïve CD4<sup>+</sup>T cells were triggered for Th17 differentiation, and TA3 (5 or 10 μM) was used to treat cells during induction of Th17 differentiation.</p><p><strong>Results: </strong><i>In vivo</i> experiments showed that TA3 decreased airway inflammation, goblet cell and smooth muscle hyperplasia, α-smooth muscle actin and collagen deposition, Th17 differentiation, and STAT3/RORγt signaling activation in mice exposed to OVA. The inhibitory effect of TA3 on STAT3/RORγt signaling activation was also observed in <i>in vitro</i> experiments. Compared to positive control static (a specific inhibitor of STAT3), TA3 had a similar effect on Th17 differentiation.</p><p><strong>Discussion: </strong>These findings indicate that TA3 may ameliorate Th17 cell differentiation by suppressing STAT3/RORγt signaling. Our data provide evidence of the potential benefits of TA3 for the treatment of asthma.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004844","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}
Dan Song, Wenfeng Wei, Jie Zhang, Lu Zhang, Weiming Wang, Jinhai Huo
{"title":"The Mechanism of Baicalin in the Treatment of Mycoplasma Pneumoniae Pneumonia by Regulating NLRP3/Caspase-1 Signaling Pathway.","authors":"Dan Song, Wenfeng Wei, Jie Zhang, Lu Zhang, Weiming Wang, Jinhai Huo","doi":"10.1080/08820139.2025.2450244","DOIUrl":"https://doi.org/10.1080/08820139.2025.2450244","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the mechanism of baicalin (BIA) attenuating the inflammatory response and lung injury in mycoplasma pneumoniae pneumonia (MPP) mice.</p><p><strong>Methods: </strong>MPP mouse models were established and then treated with BIA, azithromycin, or NLRP3 inflammasome activator. Lung wet-to-dry weight (W/D) ratio were weighed. Serum levels of MP-IgM, C-reactive protein (CRP) and bronchoalveolar lavage fluid (BALF) protein were detected by kits, NLRP3/Caspase-1 pathway-related protein levels by Western blot, and IL-1β, IL-18, IL-6 and TNF-α levels by ELISA. HE staining was performed to detect lung injury.</p><p><strong>Results: </strong>MPP mice showed elevated mouse lung W/D ratio, upregulated serum MP-IgM and CRP levels and BALF protein, and enhanced IL-6 and TNF-α levels, which were reversed by BIA or azithromycin treatment, suggesting that BIA attenuated pulmonary inflammatory response in MPP mice. The lung tissue of MPP mice showed upregulated NLRP3, cleaved Caspase-1,Caspase-1, GSDMD-N and GSDMD levels and raised IL-1β and IL-18 levels, and changes were annulled by BIA or azithromycin treatment, suggesting that BIA inhibited the NLRP3/Caspase-1 pathway activation. NLRP3/Caspase-1 pathway activation partially abrogated the alleviative effect of BIA on the pulmonary inflammatory response of MPP mice.</p><p><strong>Conclusion: </strong>BIA mitigates inflammatory response and lung injury in MPP mice by inhibiting NLRP3/Caspase-1 pathway activation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-13"},"PeriodicalIF":2.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948205","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}
Éssia de Almeida Lima, Luiz Henrique Agra Cavalcante-Silva, Deyse Cristina Madruga Carvalho, Mariana Mendonça Soares, Anna Beatriz Araujo Medeiros, Chaquip Daher Netto, Paulo Roberto Ribeiro Costa, Sandra Rodrigues-Mascarenhas
{"title":"Immunomodulatory Effects of Pterocarpanquinone LQB-118 in Murine Peritoneal Macrophages.","authors":"Éssia de Almeida Lima, Luiz Henrique Agra Cavalcante-Silva, Deyse Cristina Madruga Carvalho, Mariana Mendonça Soares, Anna Beatriz Araujo Medeiros, Chaquip Daher Netto, Paulo Roberto Ribeiro Costa, Sandra Rodrigues-Mascarenhas","doi":"10.1080/08820139.2025.2449949","DOIUrl":"https://doi.org/10.1080/08820139.2025.2449949","url":null,"abstract":"<p><strong>Background: </strong>Phagocytosis is an important function of macrophages. However, when it's dysregulated, it could compromise homeostasis. Thus, this study aimed to assess the inhibitory activity of pterocarpanquinone LQB 118 on murine macrophage phagocytosis.</p><p><strong>Methods: </strong>We used peritoneal macrophages isolated from mice to evaluate the impact of LQB 118 (5 μM) on the modulation of phagocytic activity and possible action mechanism related: IL-12 (by ELISA), NO (by Griess reaction),ROS production (by flow cytometry), and intracellular signaling proteins (iNOS, P-Akt, P-mTOR, NF-κB, and P-NF-κB) (by flow cytometry).The macrophages were stimulated with zymosan to assess both phagocytic activity and flow cytometry assays.</p><p><strong>Results: </strong>Treatment with LQB 118 resulted in a reduction in the phagocytosis of zymosan particles by macrophages. This effect could potentially be attributed to LQB's inhibition of IL-12 production and mTOR/NF-κB signaling. Furthermore, LQB 118 decreased the levels of ROS and NO without interfering with iNOS and Akt activation.</p><p><strong>Conclusion: </strong>These findings show the anti-phagocytic activity of LQB 118 on macrophage, highlighting the potential of this compound as a candidate for modulating macrophage-driven inflammation.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948123","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":"3D Bioprinting of Pig Macrophages and Human Cells Discovered the P2Y14 Receptor as a Mediator of Xenogenic Immune Responses.","authors":"Hyungkuen Kim, Sung-Jo Kim","doi":"10.1080/08820139.2024.2411388","DOIUrl":"10.1080/08820139.2024.2411388","url":null,"abstract":"<p><strong>Background: </strong>The survival rate of pig lung xenotransplantation (PLXTx) recipients is severely limited by intense xenogenic immune responses, necessitating further insights into xenogeneic immunity and the development of models to study the PLXTx immune response.</p><p><strong>Methods: </strong>We identified regulators of PLXTx immune response Using Gene ontology analysis. We assessed the metabolic changes and protein levels in 3D4/31 pig alveolar macrophages (PAMs) through flow cytometry and immunoblotting. To induce a xenogenic immune response, we co-cultured 3D4/31-PAMs with A549 human alveolar epithelial cells and evaluated cytokine expression using qRT-PCR.</p><p><strong>Results: </strong>Gene ontology analysis identified STAT1 and alveolar macrophages as contributors to lung autoimmunity and transplant rejection. In 3D4/31-PAMs, phorbol myristate acetate-induced glycogen accumulation and cyclooxygenase-2 expression were inhibited by the P2Y<sub>14</sub> inhibitor PPTN. Co-culturing 3D4/31-PAMs with A549 human alveolar epithelial cells via 3D bioprinting resulted in a more pronounced inflammatory response than 2D co-culture, with increased expression of genes related to the P2Y<sub>14</sub> cascade and inflammation. This inflammatory gene expression was prevented by PPTN treatment.</p><p><strong>Conclusion: </strong>Based on these results, we propose alginate bioprinting as an <i>in vitro</i> model for PLXTx and suggest that P2Y<sub>14</sub> is a key regulator of xenogeneic immune responses in PAMs.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"18-33"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361459","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":"Novel Serum Markers that Distinguish Behcet's Disease from Idiopathic Recurrent Aphthous Stomatitis.","authors":"Mengya Zhu, Xinliang Mao, Xianqian Huang, Minzhi Gan, Keyue Zhang, Yong Chen","doi":"10.1080/08820139.2024.2410743","DOIUrl":"10.1080/08820139.2024.2410743","url":null,"abstract":"<p><strong>Background: </strong>Behcet's disease (BD) is a rare and recurrent autoinflammatory disorder characterized by systemic vasculitis, frequently manifested as recurrent aphthous stomatitis (RAS). We aim to identify specific serum proteins to discriminate between BD and idiopathicRAS.</p><p><strong>Method: </strong>Peripheral blood was collected from 12 BD patients, 12 idiopathic RAS patients, and 21 healthy volunteers. The serum samples underwent Tandem Mass Tag-based mass spectrometry analysis. Differentially expressed proteins (DEPs) were identified for KEGG pathway enrichment, Gene Ontology (GO), and protein-protein interaction (PPI) analyses. ELISA was utilized to verify two BD-specific DEPs in another cohort consisting of 18 BD patients, 18 idiopathic RAS patients, and 18 controls.</p><p><strong>Results: </strong>Compared with RAS serum, BD serum showed 242 DEPs. 49 proteins were differentially expressed in BD but not RAS serum compared to healthy controls. KEGG pathway and GO analyses revealed that DEPs in BD and RAS have similar biological functions and cellular distributions, featuring a significant association with pathways regulating blood coagulation and immune response. When comparing DEPs between BD and RAS, several keratins emerged as markers that distinguish RAS from BD. We also identified multiple DEPs in BD but not RAS patients. PPI analysis uncovered that lipoprotein metabolism regulators serve as hub proteins, indicating their potentially essential roles in BD pathology. In addition, ELISA results confirmed the elevated LRG1 and SOD3 levels in BD, but not RAS patients, compared to healthy donors.</p><p><strong>Conclusion: </strong>Our data uncovered novel serum proteins that distinguish BD from RAS, which may potentially be useful in BD diagnosis and treatment.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361460","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":"IRF3 Promotes Asthma Pathogenesis by Regulating Type 2 Innate Lymphoid Cells.","authors":"Zihao Liang, Zixin Chen, Jinwei Chen, Yunfan Zhou, Hua Chen, Meimei Gu, Dehong Yan, Qiong Yang","doi":"10.1080/08820139.2024.2418935","DOIUrl":"10.1080/08820139.2024.2418935","url":null,"abstract":"<p><strong>Background: </strong>Allergic asthma is characterized by airway hyperresponsiveness triggered by inhaled allergens. Type 2 innate lymphoid cells (ILC2s) have been demonstrated to play a crucial role in promoting airway inflammation through the secretion of type 2 effector cytokines. However, the mechanisms underlying the functions of lung ILC2s remain unclear.</p><p><strong>Methods: </strong>In this study, we investigated the expression of <i>IRF3</i> in ILC2s in both human patients and mouse models of asthma. We utilized <i>IRF3</i>-deficient mice to assess the impact of <i>IRF3</i> deficiency on ILC2 function in a model of IL33-induced asthma. Additionally, we explored the mechanisms underlying <i>IRF3</i>-mediated regulation of ILC2s, focusing on the involvement of the transcription factor Gata3.</p><p><strong>Results: </strong>Our findings revealed elevated expression of <i>IRF3</i> in ILC2s of patients and mice with asthma, suggesting a potential role for <i>IRF3</i> in the pathogenesis of allergic asthma. Furthermore, we demonstrated that <i>IRF3</i> deficiency impairedthe expansion and function of ILC2s in IL33-induced asthma, highlighting the importance of <i>IRF3</i> in regulating ILC2-mediated responses. Importantly, we showed that the regulation of ILC2s by <i>IRF3</i> was independent of Th2 cells and mediated by the transcription factor Gata3.</p><p><strong>Conclusion: </strong>This study identifies <i>IRF3</i> as a novel regulator of lung ILC2s and suggests its potential as a promising immunotherapeutic target for allergic asthma. These findings shed light on the intricate mechanisms underlying asthma pathogenesis and provide insights into potential strategies for the development of targeted therapies for this prevalent airway disease.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"83-96"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521815","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 Physiological and Therapeutic Role of CD47 in Macrophage Function and Cancer.","authors":"Shelby N Bess, Matthew J Igoe, Timothy J Muldoon","doi":"10.1080/08820139.2024.2415409","DOIUrl":"10.1080/08820139.2024.2415409","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy is an emerging strategy in cancer therapeutics aimed at modulating the immune system to inhibit pro-tumor pathways and increase a tumor's sensitivity to chemotherapy. Several clinically approved immunotherapy treatments, such as monoclonal antibody treatments, have been successful in solid tumors such as breast, colorectal, and pancreatic. However, an outstanding challenge of these strategies is tumor cell resistance. One target of interest for immune cell modulation is targeting macrophages that enter the tumor microenvironment. More specifically, an immune checkpoint of interest is CD47. CD47 is a transmembrane protein that inhibits phagocytic activity by acting as a \"don't eat me\" signal. In both mice and humans, healthy cells can express CD47, while solid malignancies like colorectal and breast cancer express it most strongly.</p><p><strong>Methods: </strong>Analysis of literature data on the physiological and functional roles of tissue-resident macrophages, along with the structure and mechanisms of action of the CD47 pathway was explored. We also explored how CD47 can influence different aspects of the tumor microenvironment (i.e. cellular metabolism and hypoxia) in addition to current clinical strategies and challenges associated with targeting CD47.</p><p><strong>Results: </strong>Overall, it was discovered that CD47 is overexpressed in a variety of cancer types in addition to normal tissue, making it a promising treatment regimen to enhance the capability of macrophages to phagocytose tumor cells. However, treatment efficacy is varied in pre-clinical and clinical models due to various challenges such as off-target effects.</p><p><strong>Conclusion: </strong>This review emphasizes the diverse functionality of macrophages in normal and cancerous tissue, while also emphasizing the importance of macrophage targeting and their clinical significance.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"112-146"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zahra Mozooni, Fatemeh Faraji, Sara Minaeian, Leyla Bahadorizadeh
{"title":"The Relationship Between Serum IgE Level and IL-4 and IL-13 Cytokines in Colorectal Cancer Patients.","authors":"Zahra Mozooni, Fatemeh Faraji, Sara Minaeian, Leyla Bahadorizadeh","doi":"10.1080/08820139.2024.2414091","DOIUrl":"10.1080/08820139.2024.2414091","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the most common malignancy of the digestive system in the world. Immune cells and molecules in tumor microenvironment are crucial.Identifying immune system components in cancer aids in biomarker discovery. This study investigated the serum IgE levels and expression of IL-4 and IL-13 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors.</p><p><strong>Materials and methods: </strong>Thirty-six patients with CRC and 36 healthy individuals were involved in the study. Tissues and blood samples were collected. Serum levels of IgE and IL-4 and IL-13 were analyzed using the ELISA method. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the cytokines in CRC tissue samples in comparison with the adjacent control tissue.</p><p><strong>Results: </strong>Our results revealed that the serum level of IL-4 and IL-13 and also their gene expression levels were significantly decreased in CRC patients compared to the controls. The results of this study revealed that there is no significant difference in the serum levels of IgE between CRC patients and the control group.</p><p><strong>Conclusion: </strong>All in all, the results of the current research suggest that the expression levels of IL-13, IL-4, and IgE vary between CRC tissue.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"34-45"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400149","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":"Cordycepin Alleviates Lipopolysaccharides-Induced Preeclampsia-Like Impairments in Rats.","authors":"Feng Jian, Xiao Zhang","doi":"10.1080/08820139.2024.2418572","DOIUrl":"10.1080/08820139.2024.2418572","url":null,"abstract":"<p><strong>Introduction: </strong>Preeclampsia is a serious pregnancy complication that can lead to life-threatening conditions such as seizures, strokes, and even death. A dysregulated inflammatory response in the placenta plays a crucial role in the development of preeclampsia. Cordycepin, known for its anti-inflammatory and antioxidant properties, was the focus of this study, which aimed to investigate its effects on preeclampsia.</p><p><strong>Methods: </strong>A preeclampsia-like rat model was established via tail vein injection of lipopolysaccharides (LPS) at a dose of 1 μg/kg in pregnant rats. These rats were then treated with cordycepin at doses of 5, 25, or 50 mg/kg from embryonic day 6 (E6) today 18 (E18). Systolic blood pressures and urinary protein levels were monitored, and pregnancy outcomes, such as fetal body length and weight, were measured. The expression of target genes or proteins was assessed by qPCR, ELISA, and Western blot.</p><p><strong>Results: </strong>Our findings revealed that cordycepin significantly reduced systolic blood pressure and proteinuria in preeclampsia-like rats. Additionally, cordycepin improved pregnancy outcomes, as shown by increased fetal body length and weight. The treatment also lowered serum sFlt-1 levels, elevated PIGF levels, decreased placental pro-inflammatory cytokine levels (IL-1β, TNF-α, IL-6, MCP-1, and MIP-2), and raised levels of anti-inflammatory cytokine IL-10 level in preeclampsia-like rats. Furthermore, cordycepin helped restore macrophage population imbalances, increasing M1-type macrophage markers (iNOS, TNF-α, and IL-1β) and reducing M2-type macrophage markers (Arg 1, IL-10, and TGF-β).</p><p><strong>Conclusion: </strong>This study suggests that cordycepin alleviates LPS-induced preeclampsia by reducing placental inflammation and correcting the M1/M2 macrophage imbalance, offering potential therapeutic benefits for managing preeclampsia.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"68-82"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568165","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}