Immunopharmacology and Immunotoxicology最新文献

{"title":"Impact of glucocorticoids on interstitial lung disease: a medical information mart for intensive care and Mendelian randomization study.","authors":"Jun Pei, Junling Lin, Yemeng Yang, Dandan Yun, Jiao Mu, Dan Liu","doi":"10.1080/08923973.2026.2671713","DOIUrl":"10.1080/08923973.2026.2671713","url":null,"abstract":"<p><strong>Background: </strong>Glucocorticoids are commonly used for treating interstitial lung disease (ILD); however, their causation with ILD is unclear.</p><p><strong>Objective: </strong>To explore the correlation of glucocorticoids and 30-day ILD mortality and to analyze their causation using Mendelian randomization (MR).</p><p><strong>Methods: </strong>ILD patients' data were extracted from the MIMIC-IV. Kaplan-Meier curves and Cox proportional hazards models assessed the relationship between glucocorticoid use and 30-day ILD mortality, including stratified analyses. The effects of different types of glucocorticoids were examined. MR analysis was conducted using Genome-Wide Association Studies data involving individuals of European ancestry to evaluate potential causal relationships between glucocorticoids, lung function parameters (FVC, FEV1, FEV1/FVC), and ILD.</p><p><strong>Results: </strong>In MIMIC-IV study, ILD patients treated with glucocorticoids exhibited significantly lower survival rates within 14-30 days compared to those without treatment (log-rank <i>p</i> < 0.001). In ILD patients with COPD, long-acting glucocorticoids (HR = 2.400, <i>p</i> = 0.031) was significantly associated with an increased 30-day mortality rate. MR analyses showed a negative causative relationship between glucocorticoids and pulmonary function parameters (FVC (OR = 0.957, <i>p</i> < 0.001), FEV1 (OR = 0.920, <i>p</i> < 0.001) and FEV1/FVC (OR = 0.920, <i>p</i> < 0.001)), indicating that glucocorticoid use may cause a decrease in lung function parameters. A positive causal relationship with ILD (OR = 1.453, <i>p</i> = 0.014) suggested that glucocorticoid use may accelerate ILD progression and affect patients' prognosis.</p><p><strong>Conclusion: </strong>Glucocorticoid use is significantly associated with increased 30-day ILD mortality, especially for men and those with comorbid COPD. Glucocorticoids may increase the risk of ILD progression through a causal mechanism, affecting patient prognosis. Future studies should explore glucocorticoids in different ILD subtypes to develop individualized strategies.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"720-728"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868208","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 zinc oxide nanoparticles on circulating neutrophils in carbon tetrachloride (CCl4) induced liver fibrosis in rats.","authors":"Sara Youssry, Amira Abd-Elfattah Darwish, Noura A Matar, Thanaa Ibrahim Shalaby","doi":"10.1080/08923973.2026.2673544","DOIUrl":"10.1080/08923973.2026.2673544","url":null,"abstract":"<p><strong>Objective: </strong>The current study aimed to evaluate the modulatory effects of chemically prepared and <i>Rhus coriaria</i> (sumac) green-synthesized zinc oxide nanoparticles (ZnO-NPs) on circulating neutrophils and the histological structure of liver in carbon tetrachloride (CCl4) treated rats.</p><p><strong>Results: </strong>CCl4 rats showed biochemical changes and histopathological damage, together with increased neutrophil markers [myeloperoxidase (MPO) and citrullinated histone (H3cit)] as well as decreased neutrophils' phagocytic activity and miR-223 expression compared to control. ZnO-NPs treatment was significantly associated with biochemical and histopathological improvement, decreased neutrophil markers, and increased both phagocytic activity and miR-223 expression. In addition, green-synthesized ZnO-NPs were associated with greater histopathological improvement and a significant increase in miR-223 expression in comparison to chemically prepared ZnO-NPs.</p><p><strong>Conclusions: </strong>It can be concluded that ZnO-NPs may have immunomodulatory effects on circulating neutrophils that have a biological impact on disease progression. In addition, green-synthesized ZnO-NPs may be more efficient than chemically synthesized ones at providing a greater modulatory effect on circulating neutrophils and better hepatoprotective effects.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"559-571"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928930","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":"Systemic administration of interleukin-10 is associated with dose-dependent toxicities in Wistar albino rats.","authors":"Charles D Kato, Dorothy Y Angom, Stevens Kisaka, Claire M Mugasa, Enock Matovu, Monica Namayanja, Patricia Nabisubi, Kenneth Ssekatawa","doi":"10.1080/08923973.2026.2688389","DOIUrl":"10.1080/08923973.2026.2688389","url":null,"abstract":"<p><strong>Background: </strong>Interleukin 10 (IL-10) is a pleiotropic cytokine associated with immunotherapy. PEGylated IL-10 (AM0010) has been suggested as a therapeutic agent and advanced to phase-II clinical trials, which raises concerns about its safety. This study aimed to establish the toxic effects associated with systemic administration of IL-10 in Wistar albino rats.</p><p><strong>Methods: </strong>Rats were randomly divided into four groups receiving a daily intramuscular administration of 0.3mls of normal saline, 500 ng/kg, 1000 ng/kg, and 2000 ng/kg of recombinant murine IL-10 for 21 days. At day 22, rats were euthanized, and blood was collected for hematological, liver, and kidney function analysis. Liver and kidney tissue sections were used for histopathology analysis.</p><p><strong>Results: </strong>Liver function results showed that levels of total bilirubin (33.63 ± 1.43 µmol/L), direct bilirubin (7.1 ± 0.21 µmol/L), Alanine Aminotransferase (39.18 ± 1.11 U/L), Aspartate Aminotransferase (35.12 ± 0.98 U/L), and Gamma-Glutamyl Transferase (38.9 ± 0.76 U/L) were all significantly higher in the 2000 ng/kg group. For renal function, significantly low values for all parameters were recorded in the high IL-10 dose groups. Increases in red blood cell numbers, monocytes, hemoglobin levels, and hematocrit were IL-10 dose dependent, with the 2000 ng/kg having the highest numbers. Tissue sections from the liver and kidney revealed alterations in organ architecture with increasing IL-10 dose, with the tissue architecture for the 500 ng/kg IL-10 group comparable to that of the negative control group.</p><p><strong>Conclusion: </strong>Our study demonstrates that a daily IL-10 dose of up to 500 ng/kg has no significant organ function and structure alterations, and above a daily dose of 1000 ng/kg, side effects begin to appear with increasing dose.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"712-719"},"PeriodicalIF":3.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258007","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":"Myricetin attenuates atrazine-induced dysregulation of the hypothalamic-pituitary-adrenal axis of rats via anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms.","authors":"Morris M Akpan, Cynthia N Ikeji, Clementina M Arije, Khadija A Mohammed, Faoziyat A Salaudeen, Isaac A Adedara, Solomon E Owumi, Ebenezer O Farombi","doi":"10.1080/08923973.2026.2662624","DOIUrl":"10.1080/08923973.2026.2662624","url":null,"abstract":"<p><strong>Background: </strong>The hypothalamic-pituitary-adrenal (HPA) axis is an important part of the stress response system that produces a biological reaction to stressful stimuli and can be activated by stressors such as atrazine. Atrazine (ATZ) is a common triazine herbicide used in the management of weeds in corn and sugarcane, and its persistence in the environment through runoff and leaching leads to frequent contamination of soil and water, with subsequent adverse health implications. Myricetin (MYR) is a biologically active compound with various pharmacological potentials against noxious agents.</p><p><strong>Objective and methods: </strong>This study evaluated the effects of MYR on the HPA axis of male Wistar rats sub-chronically exposed to atrazine (ATZ), gavaged with either atrazine (50 mg/kg), myricetin (20 mg/kg), or a combination of both for 45 consecutive days.</p><p><strong>Result: </strong>Exposure to ATZ increased serum levels of adrenocorticotropin-releasing hormone (ACTH) and corticosterone, and significantly decreased the activities of hypothalamic and adrenal antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase, reduced glutathione), and hypothalamic acetylcholinesterase (AChE). More so, ATZ-challenged rats showed increased levels of reactive oxygen species and lipid peroxidation, Nitric oxide, tumor necrosis factor-α, interleukin-1β, and caspase-3 in both tissues. Conversely, treatment with myricetin significantly restored the serum levels of ACTH and corticosterone, enhanced the antioxidant enzyme activities, reduced the oxidative-inflammatory and apoptotic markers in both tissues, and increased the hypothalamic AChE activity of the treated animals. Myricetin also reversed the histological abnormalities that atrazine elicited in the treated animals.</p><p><strong>Conclusion: </strong>Overall, MYR, through its antioxidant, anti-inflammatory, and anti-apoptotic properties, attenuated the ATZ-induced disruption of the HPA axis of rats.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"455-468"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory activity and toxicological safety of synthetic chalcone derivatives in preclinical trials.","authors":"Paula G F de Oliveira, Tainá L Lubschinski, Octavio L G Fernandes, Tiago Tizziani, Ziliani da S Buss, Louis P Sandjo, Felipe P Daltoé, Eduardo M Dalmarco","doi":"10.1080/08923973.2026.2635985","DOIUrl":"10.1080/08923973.2026.2635985","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is an essential physiological defense mechanism that aims to maintain homeostasis. However, it can lead to chronic or autoimmune diseases. The chalcones structural flexibility represents a promising class for developing new drugs and exhibits diverse activities, including anti-inflammatory effects.</p><p><strong>Material and methods: </strong>To evaluate the cell viability and anti-inflammatory potential of 23 chalcone derivative compounds by measuring nitric oxide metabolites in a model of lipopolysaccharide-stimulated J774A.1 cells. After using the acute lung injury model in mice, the acute oral toxicity of compounds with favorable <i>in vitro</i> profiles was determined according to guideline 423 of the Organization for Economic Cooperation and Development.</p><p><strong>Results: </strong>Of the compounds tested in J774A.1 cells (<i>n</i> = 23) and seventeen showed acceptable results and were subjected to nitric oxide inhibition after lipopolysaccharide stimulation; two (RX10.2 and RX10.4) compounds showed significant inhibition under this inflammatory parameter. The compounds were then tested <i>in vivo</i>. RX10.4 failed to reproduce the <i>in vitro</i> anti-inflammatory effect. Nevertheless, RX10.2 demonstrated exciting performance, reducing the leukocyte migration on the bronchoalveolar lavage by limiting neutrophil influx and exudation levels. The compound also significantly reduced nitric oxide levels and myeloperoxidase activity. Lastly, RX10.2 did not show signs of acute oral toxicity.</p><p><strong>Conclusions: </strong>RX10.2 showed important anti-inflammatory activity <i>in vitro</i> and <i>in vivo</i> without acute toxicity. This finding justifies further investigation, as it proved to be a promising prototype for developing new anti-inflammatory drugs.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"469-478"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928900","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":"Comprehensive pharmacovigilance analysis of lebrikizumab: a real-world safety assessment based on the FDA Adverse Event Reporting System (FAERS) database.","authors":"Maohua Chen, Chengjie Ke, Yaping Huang","doi":"10.1080/08923973.2026.2648209","DOIUrl":"10.1080/08923973.2026.2648209","url":null,"abstract":"<p><strong>Background: </strong>Lebrikizumab is an interleukin-13 antagonist that has been approved for use in adults and pediatric patients aged 12 years and over who weigh at least 40 kg, for the treatment of moderate-to-severe atopic dermatitis (AD) that is inadequately controlled with topical prescription therapies, or for whom such therapies are not suitable. Due to the relatively short duration of existing clinical trials and the absence of real-world postmarketing evidence involving AD patients receiving lebrikizumab, it is crucial to comprehensively characterize its safety profile, including the potential delayed adverse events (AEs).</p><p><strong>Methods: </strong>AE signals were identified using disproportionality analysis with four algorithms: the reporting odds ratio (ROR), the proportional reporting ratio, the information component, and the empirical Bayesian geometric mean. Data were analyzed from the FDA Adverse Event Reporting System, covering the period from the fourth quarter of 2024 to the third quarter of 2025.</p><p><strong>Results: </strong>A total of 791 AEs associated with lebrikizumab were identified. Lebrikizumab was documented in a lower proportion of serious AEs, accounting for 15.68% of cases. The three most frequently reported AEs associated with lebrikizumab were injection site pain, conjunctivitis, and rash. The top three AE signals with ROR values were conjunctivitis, eyelid irritation and dermatitis exfoliative generalized. Specific AEs of lebrikizumab included hypersensitivity, eosinophilia, and injection site reactions.</p><p><strong>Conclusion: </strong>This study provides a comprehensive overview of the safety of lebrikizumab and confirms that it has a favorable and manageable safety profile, supporting its suitability for long-term use in clinical practice.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"396-403"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498732","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":"Modulation of ET1/NF-κB/IL-6/STAT-4/AP-1 pathway by ambrisentan alleviates isoprenaline-induced myocardial injury.","authors":"Marwa Monier Mahmoud Refaie, Dina Ali Maher Abdel Dayem, Olivia N Beshay, Sayed Shehata, Asmaa S M Abdel Fattah, Shereen Mohammed Mohammed Elsaghir, Asmaa A Hasan, Enas Fathy, Heba A Habib, Asmaa A Muhammed, Asmaa Mohamed Mahmoud Ali, Asmaa Mohammed Hishmat","doi":"10.1080/08923973.2026.2671718","DOIUrl":"10.1080/08923973.2026.2671718","url":null,"abstract":"<p><strong>Background: </strong>Myocardial injury stands as the foremost contributing factor in raising morbidity and mortality within the realm of cardiac diseases worldwide. Nowadays, there is no available treatment to completely rescue the myocardium. Thus, we aimed to study the possible role of ambrisentan (AMB) in experimentally induced myocardial damage using a highly toxic dose of isoprenaline (ISO) (150 mg/kg).</p><p><strong>Methodology: </strong>Rats were randomly divided into five groups: control, ISO given groups, which were administered alone or in combination with AMB in three different doses (10, 20, and 30 mg/kg/day).</p><p><strong>Results: </strong>It was revealed that ISO administration could induce heart injury as confirmed by significant elevations of the cardiac enzymes, including lactate dehydrogenase (LDH), troponin I, and creatine kinase-MB (CK-MB). In addition, there are disturbed oxidative stress parameters in the form of a significant increase of malondialdehyde (MDA) but significant decreases of reduced glutathione (GSH) and total antioxidant capacity (TAC) with toxic histopathological changes and up-regulation of endothelin-1 (ET-1)/nuclear factor kappa B (NF-κB)/interleukin-6 (IL-6)/signal transducer and activator of transcription-4 (STAT-4)/activator protein-1 (AP-1) pathway. However, co-administration of AMB could ameliorate ISO-induced biochemical and histological changes.</p><p><strong>Conclusion: </strong>We concluded that AMB successfully diminished ISO-induced injury likely due to its main pharmacological action of selective inhibition on ET1A receptor, modulation of ET1/NF-κB/IL-6/STAT-4/AP-1 signaling pathways with anti-inflammatory, anti-apoptotic, and antioxidant properties.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"495-506"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941434","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":"Dapagliflozin and crocin ameliorate DOX-induced cardiotoxicity in rats via activating the Nrf-2/HO-1/NQO1 pathway: a comparative study.","authors":"Anwaar M Shaban, Eman A Ali, Marwa Mohamed Ibrahim Khalil, Marwa Omar, Yousra Ali Rohem Al-Ghalban, Eman I El-Gizawy","doi":"10.1080/08923973.2026.2648210","DOIUrl":"10.1080/08923973.2026.2648210","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin-(DOX-) related cardiotoxicity is a progressive degenerative loss of cardiac muscle mass and strength. This investigation aims to compare the anticipated cardioprotective effects of crocin (Cr) and dapagliflozin (DAPA) against DOX-induced cardiotoxicity, and to assess their effects on apoptosis and the Nrf-2/HO-1/NQO1 pathway.</p><p><strong>Materials and methods: </strong>Forty Wistar male rats were randomly divided into four groups: The control group received distilled water (DW) by oral gavage. The DOX group was given DOX 3 times/week, i.p., 2.5 mg/kg for 3 weeks. The Cr + DOX-treated group was intraperitoneally injected with Cr daily, concomitantly with DOX, for 12 weeks. The DAPA + DOX-treated group received DAPA daily by oral gavage concomitantly with DOX for 12 weeks. Initial fasting blood glucose (FBG), body weight, vital signs, systolic blood pressure (SBP), and electrocardiography (ECG) were recorded and then repeated monthly throughout the study period. After 12 weeks, biochemical analyses were performed. Moreover, histopathological and immunohistochemical examinations of cardiac tissue were conducted.</p><p><strong>Results: </strong>DOX significantly affected FBG and increased oxidative stress markers and proinflammatory cytokines, with hypotension, bradycardia, ECG changes, and downregulation of antioxidant genes (Nrf-2/HO-1/NQO1) mRNA. Besides, cardiac biomarkers deteriorated. Administration of either Cr or DAPA resulted in significant improvements in all tested parameters compared with DOX. However, the DAPA + DOX group showed greater improvement, particularly in some parameters.</p><p><strong>Conclusion: </strong>DAPA is a promising new cardioprotective medication against DOX-related cardiotoxicity. Cardiotoxicity is better controlled with DAPA than Cr by suppressing oxidative stress, apoptosis, and upregulation of the antioxidant Nrf-2/HO-1/NQO1 genes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"437-454"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498689","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":"Fluvoxamine modulates interferon and inflammatory gene signatures in immune cell lines: an <i>in silico</i> transcriptomic analysis for lupus repurposing.","authors":"Dorian Dulcic, Lucija Dumancic, Robert Marcec, Ivan Padjen, Miroslav Mayer, Robert Likic","doi":"10.1080/08923973.2026.2671719","DOIUrl":"10.1080/08923973.2026.2671719","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by chronic inflammation and dysregulated interferon (IFN) signaling. Many patients remain refractory to existing treatments, underscoring the need for novel therapeutic approaches achievable through drug repurposing. Fluvoxamine, an antidepressant with anti-inflammatory and immunomodulatory properties, has not been systematically studied in SLE.</p><p><strong>Methods: </strong>Differentially expressed genes (|Z| ≥ 2) were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Gene Set Enrichment Analysis (GSEA) was applied to assess pathway-level modulation of six hallmark SLE-related signatures.</p><p><strong>Results: </strong>Fluvoxamine induced cell line-specific transcriptomic changes. Jurkat and THP-1 cells showed strong enrichment of TNF-α/NF-κB signaling and regulation of apoptosis-related genes, while HEK293 and A549 cells displayed modulation of cytokine and fibrotic pathways, including NOS3 upregulation. U2OS cells exhibited prominent apoptotic signatures. Although hallmark interferon-α/γ responses were modestly altered at the pathway level, canonical interferon-stimulated genes (e.g. IFI44L, ISG15, MX1) were not significantly downregulated in immune-derived lines. Overall, TNF-α/NF-κB activation and apoptosis emerged as the most consistently affected pathways across models.</p><p><strong>Conclusion: </strong>This integrative transcriptomic study supports fluvoxamine as a candidate immunomodulator with potential relevance for SLE, particularly through modulation of NF-κB and apoptotic pathways. These findings provide a mechanistic rationale for further investigation of sigma-1 receptor-targeting agents in autoimmune diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"507-517"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971875","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":"Alyssin modulates inflammatory mediator expression in TNF-α-stimulated human periodontal ligament cells.","authors":"Ikuko Hosokawa, Yoshitaka Hosokawa, Risa Okamoto, Kazumi Ozaki, Keiichi Hosaka","doi":"10.1080/08923973.2026.2671723","DOIUrl":"10.1080/08923973.2026.2671723","url":null,"abstract":"<p><strong>Objectives: </strong>Alyssin is an isothiocyanate found in cruciferous plants, and it has been reported to have physiologically active effects. However, there have been no attempts to use alyssin for the treatment of periodontitis, and there are no reports investigating the effects of alyssin on periodontal tissue component cells. In this study, experiments were conducted to determine whether alyssin has an anti-inflammatory effect on human periodontal ligament cells.</p><p><strong>Methods: </strong>Cytokine production in supernatant was measured by ELISA. Activation of signal transduction pathways and intracellular protein expression were examined using the western blot analysis.</p><p><strong>Results: </strong>We found that alyssin suppressed the tumor necrosis factor (TNF)-α -induced production of interleukin (IL)-6 and C-C motif chemokine ligand (CCL)20, as well as the expression of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 in human periodontal ligament cells (HPDLCs). We also found that alyssin inhibited the TNF-α-induced activation of nuclear factor (NF)-κB, signal transducer and activator of transcription (STAT)3, and p70S6 kinase (p70S6K) in HPDLCs. Furthermore, we found that the expression of NF-E2-related factor (Nrf)2, heme oxygenase (HO)-1, and NAD(P)H quinone dehydrogenase (NQO)1, which are antioxidant enzymes, were enhanced by alyssin treatment in HPDLCs.</p><p><strong>Conclusion: </strong>This study suggests that alyssin may attenuate the expression of inflammatory mediators in human periodontal ligament cells by suppressing the activation of NF-κB, STAT3 and p70S6K. Alyssin also increases the expression of antioxidant enzymes.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"518-524"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868176","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}