Particle and Fibre Toxicology最新文献

{"title":"Repeated air pollution exposure predisposes to adverse outcomes from acute lung injury.","authors":"Chiara Monge, Nairrita Majumder, Ian Cumming, Habibul Hasan Mazumder, Yulu Li, William Travis Goldsmith, Panchalee Mahavithana, Anand Ranpara, Robert M Tighe, Jack R Harkema, Salik Hussain","doi":"10.1186/s12989-026-00686-5","DOIUrl":"10.1186/s12989-026-00686-5","url":null,"abstract":"<p><strong>Background: </strong>Air pollution exposure is associated with increased risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). While the possibility of air pollution priming the immune system to exacerbate ALI is postulated, it lacks experimental evidence. NOD-like Receptor X1 (NLRX1) is a mitochondria-localized protein that regulates a variety of cellular functions including inflammation and oxidant generation. Presently, the role of NLRX1 in the context of air pollution-mediated priming of ALI remains unclear. We hypothesized that a subacute ozone (O₃) and ultrafine carbon black (CB) mixed inhalation exposure would prime for worse ALI responses and NLRX1 would exert a protective role. We exposed male C57BL/6J (Nlrx1^+/+) and Nlrx1^-/- mice to a mixture of 250 ppb O₃ and 1 mg/m³ CB 3 hours per day for 5 days a week over 3 weeks by whole body inhalation. After 3 weeks of exposure, we induced ALI by administering 1.5 IU/Kg bleomycin (BLM) and euthanized mice 14 days post-BLM exposure. We assessed survival, lung function, inflammation, lung remodeling and proportions of immune cells.</p><p><strong>Results: </strong>In Nlrx1^-/- mice air pollution exposure primed for worsened bleomycin-induced survival. The adverse phenotype in Nlrx1^-/- mice was associated with increased inflammation, greater lung function decline and increased collagen deposition. Immune cell phenotyping indicated modulation of macrophages (alveolar and interstitial), neutrophils and CD103⁺ dendritic cells in Nlrx1^-/- exposed and BLM challenged mice.</p><p><strong>Conclusions: </strong>We identify NLRX1 as a novel mediator for air pollution-induced priming of worsened ALI.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cu(OH)₂ nanopesticide triggered heart failure-like pathogenesis in mice by potentially targeting mmu-miRNA-590-3p and mmu-miRNA-338-5p in Wnt/β-catenin signaling.","authors":"Zhihua Ren, Yixue Cai, Yonghui Duan, Xiao Wang, Jiafei Sun, Danqin Ren, Jiefeng Liang, Tingting Ku, Xia Ning, Nan Sang","doi":"10.1186/s12989-026-00683-8","DOIUrl":"10.1186/s12989-026-00683-8","url":null,"abstract":"<p><strong>Background: </strong>Nanopesticides have been progressively incorporated into contemporary agricultural systems owing to their distinctive physicochemical characteristics and superior pest management capabilities. Given their environmental persistence and propensity for bioaccumulation, nanopesticides are increasingly recognized as emerging cardiovascular toxicants, thus warranting systematic investigation of their exposure-associated cardiotoxic effects.</p><p><strong>Methods: </strong>In the present study, the impact of Cu(OH)₂ nanopesticide on cardiac homeostasis was systematically investigated in a C57BL/6 mouse model following one-month exposure administered via oral gavage, with copper concentrations set at 0 (vehicle control), 1, and 5 mg/kg bw. Multiple molecular biology techniques were employed to elucidate the nanopesticide-induced cardiac impairment and the underlying mechanisms.</p><p><strong>Results: </strong>It was demonstrated that prolonged exposure to this copper-based nanopesticide resulted in significant deterioration of ventricular systolic and diastolic function, induction of ventricular chamber remodeling, disturbance of hemodynamic stability, and dysregulation of cardiac substructural gene expression, collectively mirroring the characteristic phenotypic manifestations and underlying molecular hallmarks of clinical heart failure. The dysregulation of Cu(OH)₂ nanopesticide in the Wnt/β-catenin signaling pathway through the targeting of mmu-miRNA-590-3p and mmu-miRNA-338-5p provided a proposed explanation for the underlying mechanism of the nanopesticide-induced imbalance of cardiac homeostasis.</p><p><strong>Conclusion: </strong>The present findings provide new insights into the cardiovascular hazards posed by Cu(OH)₂ nanopesticide, advancing the development of a more rigorous risk assessment protocol for this emerging category of agricultural nanomaterial.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary toxicity of brake wear particles: effects of composition and surface reactivity.","authors":"Gyuri Kim, Soyeon Jeon, Tae Hwan Shin, Yonghyeon Park, Kiyun Kim, Sang-Hee Woo, Yun Suk Huh, Joon-Goo Lee, Seokhwan Lee, Wan-Seob Cho","doi":"10.1186/s12989-026-00684-7","DOIUrl":"10.1186/s12989-026-00684-7","url":null,"abstract":"<p><strong>Background: </strong>Airborne brake wear particles (BWPs) are increasingly recognized as important non-exhaust contributors to urban particulate pollution; however, their inhalation toxicity and the key determinants of their pulmonary effects remain poorly defined.</p><p><strong>Results: </strong>Two types of BWPs were generated using a brake dynamometer equipped with non-asbestos organic (NAO) and low-metallic (LM) brake pads on a cast-iron disc. The ≤ 2.5 μm fractions of BWPs generated from the NAO and LM brake pads were designated NAO_2.5 and LM_2.5, respectively. SRM 2975 (diesel exhaust particles) and Fe₂O₃ nanoparticles were included as reference particles. The test particles were characterized for their physicochemical properties, including morphology, size, surface area, crystallinity, colloidal properties, chemical composition, and solubility. The intrinsic oxidative potentials (IOPs) of the test particles, evaluated using a cell-free 2',7'-dichlorodihydrofluorescein diacetate assay, ranked as NAO_2.5 > SRM 2975 > LM_2.5 > Fe₂O₃ on a mass basis, and as NAO_2.5 > LM_2.5 > SRM 2975 > Fe₂O₃ on a surface area basis. Pulmonary neutrophilic inflammatory responses were evaluated by bronchoalveolar lavage fluid analysis at 24 h after pharyngeal aspiration of 25, 50, and 100 µg/mouse in female BALB/c mice. On a mass basis, the inflammatory response ranked SRM 2975 > NAO_2.5 > Fe₂O₃ > LM_2.5 on a mass basis, whereas on a surface area basis, the ranking was NAO_2.5 > LM_2.5 > SRM 2975 > Fe₂O₃. Lung burden analysis at days 0, 1, and 28 after a single pharyngeal aspiration of 100 µg/mouse showed relatively higher 28-day retention of NAO_2.5 and LM_2.5 (approximately 75% and 67%, respectively) compared to that of SRM 2975 (47%).</p><p><strong>Conclusions: </strong>These data indicate that NAO_2.5 is more inflammogenic than LM_2.5. Given that BWPs were larger and had substantially lower surface area than the reference particles, their stronger responses under surface area-based comparison suggest greater inflammatory potency per unit surface area. Overall, the BWPs examined in this study exhibited a toxicity profile not fully explained by IOP alone, suggesting an important contribution of particle-specific physicochemical properties.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultraviolet irradiation-induced enhancement of inflammatory potential of polystyrene nano- and microplastics and effects of dispersion on lung clearance.","authors":"Yeonjeong Ha, Jun Hui Jeon, Eunsol Bae, Songyeon Kim, Gyuri Kim, Soyeon Jeon, So-Young An, Hyeong-Gyu Lim, Sung Ik Yang, Wan-Seob Cho","doi":"10.1186/s12989-026-00680-x","DOIUrl":"10.1186/s12989-026-00680-x","url":null,"abstract":"<p><strong>Background: </strong>Microplastics are pervasive environmental pollutants that pose potential risks to human health, particularly through inhalation. Despite growing concerns, limited data exist on how environmental aging, such as ultraviolet (UV) irradiation, affects the pulmonary toxicity of inhaled nano- and microplastics. This study evaluated the influence of UV-driven surface oxidation on the inflammatory potential and lung clearance kinetics of polystyrene (PS) particles. Spherical PS particles (50, 200, and 400 nm) were synthesized, selectively oxidized by UV irradiation, and thoroughly characterized for surface chemistry and intrinsic reactive oxygen species (ROS) generation.</p><p><strong>Results: </strong>Mice exposed to these particles via pharyngeal aspiration (75 µg/mouse; n = 4 per group) exhibited significantly greater acute pulmonary inflammation from UV-oxidized particles compared to pristine particles, with smaller ones (50 nm) displaying slightly higher inflammogenicity. Although inflammation largely resolved by four weeks post-exposure (75 µg/mouse; n = 4 per group), mild neutrophilic inflammation persisted. Notably, particle-induced ROS generation and subsequent cellular oxidative stress in alveolar macrophages showed strong correlations with acute inflammatory endpoints. Additionally, the particle dispersion method significantly affected lung clearance rates: particles dispersed in distilled water (DW) containing 10% ethanol exhibited shorter clearance half-lives (3-8 days) than those dispersed in 5% mouse serum (~ 18 days) (75 µg/mouse; n = 4 per group). These results highlight the dispersion medium as an important experimental variable influencing pulmonary clearance and toxicity interpretation.</p><p><strong>Conclusions: </strong>These findings suggest that the surface oxidation of nano- and microplastics through environmental aging can increase associated health risks. However, within the tested size range (50-400 nm), neither surface oxidation nor particle size markedly altered the overall lung clearance pattern.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polystyrene microplastics and hepatic fibrosis-related indices in type 2 diabetes: a cross-sectional analysis with experimental validation.","authors":"Ying Sun, Xiaoqin Xu, Guoting Sun, Jiang Li, Bowei Yu, Yuying Wang, Kun Zhang, Fangzhen Xia, Yingli Lu, Ningjian Wang","doi":"10.1186/s12989-026-00681-w","DOIUrl":"10.1186/s12989-026-00681-w","url":null,"abstract":"<p><strong>Background: </strong>Microplastics (MPs) are emerging environmental contaminants with potential hepatotoxicity, yet direct epidemiological evidence linking internal MP exposure to liver injury is scarce, particularly in individuals with type 2 diabetes (T2D). In this cross-sectional study nested within the METAL2 cohort, we aimed to characterize blood microplastic profiles in patients with T2D and to determine whether specific MP polymers are associated with hepatic steatosis and fibrosis risk, with experimental validation of the identified polymer.</p><p><strong>Results: </strong>In patients with T2D, multiple MP polymers were detectable in blood, with polyvinyl chloride (PVC), polyamide 66 (PA66), and polystyrene (PS) being the most prevalent. Although PVC constituted the largest proportion of total MP burden, PS showed the most consistent nominal positive liver-related signal in the human analyses, including higher levels in participants with elevated fibrosis risk and higher FIB-4 and ALT in the highest exposure quartile. Experimental validation in diabetic mice demonstrated that PS microplastics markedly exacerbated hepatic steatosis, inflammation, and collagen deposition, leading to overt liver fibrosis. Mechanistically, PS-MPs exposure disrupted hepatic lipid homeostasis and concurrently activated the NLRP3 inflammasome and the TGF-β1/Smad signaling pathway, promoting inflammatory amplification and hepatic stellate cell activation.</p><p><strong>Conclusion: </strong>This integrated human and experimental study provides preliminary evidence that circulating PS-associated signals are linked to liver-related indices in T2D, while experimental findings support the biological plausibility that PS exposure may aggravate hepatic injury under diabetic conditions.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial NLRP3 drives silica-induced lung injury and fibrosis through IL-18 and pro-fibrotic neutrophil recruitment.","authors":"Maggie Lam, Kristian T Barry, Christopher J Hodges, Alison C West, Christopher M Harpur, Ashley Mansell, Michelle D Tate","doi":"10.1186/s12989-026-00682-9","DOIUrl":"10.1186/s12989-026-00682-9","url":null,"abstract":"<p><strong>Background: </strong>Silicosis is a progressive inflammatory and fibrotic lung disease with no effective treatments beyond symptom management. While global NLRP3 inflammasome deficiency attenuates silica-induced pathology, myeloid-specific Nlrp3 deletion provides no protection, suggesting that other cellular sources drive disease. Given that epithelial cells directly encounter inhaled silica particles and express NLRP3, we investigated the functional contribution of epithelial Nlrp3 to silicosis pathogenesis.</p><p><strong>Results: </strong>Using inducible epithelial-specific knockout models, we found that alveolar epithelial (Sftpc⁺) cells drive early caspase-1 activation and airway IL-18 production, while partially reducing tissue IL-1β maturation. Loss of alveolar epithelial Nlrp3 limited recruitment of pro-fibrotic Siglec-F⁺ neutrophils, which expressed elevated fibrogenic mediators, and reduced airway neutrophil elastase levels. At day 14, Nlrp3 deficiency reduced persistent Siglec-F⁺ neutrophils and broadly reduced airway inflammatory cytokines, accompanied by decreased lung damage, alveolitis, collagen deposition, fibrotic nodule expansion, and α-SMA expression, independent of detectable TGFβ changes. By day 28, during the chronic fibrotic phase, alveolar epithelial Nlrp3 deficiency continued to confer protection, reducing persistent inflammation, collagen accumulation, and fibrotic nodule size. In parallel, deletion of Nlrp3 in Scgb1a1⁺ bronchiolar epithelial cells reduced early inflammasome activation at day 3 and similarly decreased chronic lung inflammation, collagen deposition, and fibrotic nodule expansion, without affecting nodule number or cellularity at day 28.</p><p><strong>Conclusions: </strong>These findings establish epithelial Nlrp3 as a critical driver of silica-induced fibrotic remodeling through IL-18 and pro-fibrotic neutrophil recruitment, independent of canonical TGFβ mechanisms. This epithelial-centric paradigm provides a rationale for precision therapeutic strategies targeting epithelial NLRP3.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147819317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to polylactic acid microplastics during puberty increases the risk of skeletal dysplasia by disrupting arachidonic acid metabolism in osteoblasts.","authors":"Yao Zhang, Zongheng Cai, Xinyu Luo, Hao Chen, Xing Zhang, Chun Pan","doi":"10.1186/s12989-026-00679-4","DOIUrl":"10.1186/s12989-026-00679-4","url":null,"abstract":"<p><p>Biodegradable polylactic acid (PLA) plastic is considered to be an effective method to solve the global white pollution caused by petroleum-based plastics. Its wide application in disposable tableware and food packaging has led to the risk of human exposure to PLA microplastics (MPs), but its impact on bone health is unclear. Our study investigated the skeletal developmental toxicity of PLA-MPs at environmentally accessible concentrations in adolescent mice and its potential mechanism. Here we demonstrated that PLA-MPs treatment in adolescent mice showed significant skeletal developmental toxicity, manifested as shortened body length and slowed growth of femur and tibia. Further analysis found that PLA-MPs caused a diminution of epiphyseal plate thickness, a decrement in the count of bone trabeculae, damaged femoral microstructure, and inhibited femoral new bone formation. Notably, PLA-MPs enter osteoblasts and destroy their osteogenic differentiation, resulting in a dose-dependent damage that reduces the formation of calcium nodules. Transcriptome analysis further demonstrated that PLA-MPs exposure was associated with disrupted arachidonic acid metabolism, which may contribute to impaired osteoblast formation, especially Cyp2j5 gene and its downstream metabolite epoxyeicosatrienoic acids were significantly inhibited. Subsequent studies have indicated that Ophiopogonin D (Oph D) can activate Cyp2j5 signal to alleviate PLA-MPs-induced damaged osteoblast differentiation. Furthermore, alleviating impaired differentiation function of osteoblasts using Oph D can significantly improve the reduction of trabecular bone and bone microstructure damage caused by adolescent PLA-MPs exposure. This study not only identifies a potential mechanistic association between PLA-MPs exposure and poor bone development, but also emphasizes the need for targeted interventions to protect bone health in adolescent children and the broader impact on environmental and public health policies.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated aquatic aging exacerbates pulmonary toxicity of graphite nanoplatelets by mechanically and chemically induced surface oxidation, enhancing oxidative potential.","authors":"Karthika Viswanathan, Youn-Joo Jung, Maruthupandy Muthuchamy, Soyeon Jeon, June-Woo Park, Wan-Seob Cho","doi":"10.1186/s12989-026-00678-5","DOIUrl":"10.1186/s12989-026-00678-5","url":null,"abstract":"<p><strong>Background: </strong>Graphite nanoplatelets (GNPs) are increasingly used in advanced materials, yet their environmental transformation and resulting health impacts remain poorly understood. This study investigated how long-term aquatic aging alters the physicochemical properties and pulmonary toxicity of GNPs.</p><p><strong>Results: </strong>Pristine GNPs (PGNPs) were aged for 26 months in water containing sand under constant agitation to simulate natural mechanical and chemical weathering, yielding aged GNPs (AGNPs) with increased surface oxidation level, smaller lateral dimensions, and improved hydrophilicity. These alterations enhanced the intrinsic oxidative potential of AGNPs by 1.28-1.40-fold relative to PGNPs. Following a single intratracheal instillation in mice (25-100 µg/mouse), AGNPs induced significantly stronger pulmonary inflammation at both 24 h and 7 days, characterized by elevated neutrophil infiltration, increased levels of lactate dehydrogenase, total protein, and pro-inflammatory cytokines in bronchoalveolar lavage fluid. Although both materials showed a similar clearance pattern, AGNPs showed a slightly prolonged retention compared to PGNPs (half-life: AGNPs 10 days, PGNPs 5.5 days). Differentiated THP-1 macrophages and A549 cells exposed to AGNPs showed higher cytotoxicity, intracellular reactive oxygen species (ROS) generation, and cytokine release than PGNPs, confirming the in vivo findings. Correlation analysis revealed that ROS levels were strongly associated with inflammatory and cytotoxic endpoints (Pearson r > 0.90), indicating that oxidative stress is a key mechanism of GNP-induced toxicity.</p><p><strong>Conclusions: </strong>These findings demonstrate that simulated aquatic aging enhances the oxidative potential and pulmonary toxicity of GNPs through mechanically and chemically induced surface oxidation, highlighting the need to consider environmental transformation in nanomaterial hazard assessment and life-cycle-based safety assessment.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aged automobile cabin air filters as secondary pollution sources: mechanistic insights into NLRP3 inflammasome activation and discovery of a natural inhibitor.","authors":"Jiaqi Tian, Yi Guan, Zengfeng Li, Qiang Li, Dandan Song, Ning Li, Xiaotan Shi, Yongfei Zheng, Shuyin Duan, Lin Zhang","doi":"10.1186/s12989-026-00674-9","DOIUrl":"10.1186/s12989-026-00674-9","url":null,"abstract":"<p><p>Automobile cabin air filter-deposited particulate matter represents an underappreciated exposure source, yet the differential toxicity between filter sides and underlying mechanisms remain unclear. Here, we systematically investigated particles extracted from the inside (cabin-facing) and outside (environment-facing) membranes of used automobile air filters. Morphological analysis revealed that inside particles exhibited smaller size and greater dispersion, consistent with ultrafine particle enrichment. In a murine exposure model, inside particles induced more severe pulmonary inflammation, histopathological injury, and elevated interleukin-1β levels compared to outside particles at equivalent doses. Single-cell RNA sequencing identified alveolar macrophages as the predominant responding cell type, with significant enrichment of the NOD-like receptor signaling pathway. Mechanistic investigations demonstrated that particle exposure activated the NLRP3 inflammasome and triggered Gasdermin D-mediated pyroptosis through a reactive oxygen species-independent pathway. Furthermore, we employed structure-based virtual screening of over two thousand natural compounds, from which we identified the cyclic dipeptide Cyclo-(Tyr-Phe) as a novel NLRP3 inhibitor. Molecular dynamics simulations and cellular thermal shift assays confirmed direct NLRP3 binding, while functional validation demonstrated that Cyclo-(Tyr-Phe) effectively attenuated particle-induced pyroptosis and inflammatory responses. These findings illuminate the heightened toxicity of ultrafine-enriched filter particles and provide a promising therapeutic candidate for mitigating particle-induced lung injury.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pollutant particles enhance house dust mite induced type 2 inflammation and the recruitment of monocyte derived Cd11c⁺ Gpnmb⁺ macrophages to the airway lumen.","authors":"Kirsty Meldrum, Ayokulehin Muse Kosoko, Martin Oliver Leonard","doi":"10.1186/s12989-026-00675-8","DOIUrl":"10.1186/s12989-026-00675-8","url":null,"abstract":"<p><strong>Background: </strong>Air pollution particles exacerbate allergic asthma and can enhance inflammatory responses to allergen exposure, but the cellular mechanisms involved remain incompletely defined. We examined how diesel exhaust particles (DEP) enhance house-dust-mite (HDM) inflammatory responses within the lung and characterised potential mechanisms that may contribute to enhanced type 2 (T2) inflammatory responses.</p><p><strong>Results: </strong>In mice subjected to repeated intranasal exposures, DEP alone had modest effects, whereas DEP + HDM markedly increased type-2 inflammatory indicators (Serum IgE; Airway Il13, Il4 & Tslp) and eosinophilia alongside expansion of Th2 cells. Bulk transcriptomics showed far stronger differential expression in luminal airway cells than tissue, with a DEP + HDM-specific signature enriched for mast cells, alternatively activated macrophages (AAM), and B-cells in the lumen. Combined single-cell proteomic and transcriptomic profiling identified an expanded Cd11c⁺, SiglecF⁻, Apoe⁺, Gpnmb⁺ monocyte-derived macrophage subset (RM.Gp2), which showed increased type 2 chemokines Ccl8 and Ccl24 with DEP + HDM compared to HDM alone. Trajectory analysis placed RM.Gp2 downstream of Ccr2⁺ monocyte derived population, and protein/mRNA data supported a Ccl2-Ccr2-dependent influx that enlarges the RM.Gp2 pool. High-content imaging confirmed increased RM.Mo and RM.Gp2 numbers and higher total luminal Ccl8/Ccl24. F4/80⁺ luminal airway macrophages isolated from DEP pre-treated mice, demonstrated enhanced upregulation of Ccl8 and Ccl24 mRNA in response to ex vivo Il-4/Il-13 treatment, compared to macrophages isolated from control mice. Examination of an additional particle type (CeO₂ Nanoparticles) in the same exposure model, revealed a shared luminal transcriptomic response and AAM/chemokine programme as with DEP.</p><p><strong>Conclusions: </strong>Our data suggests that pollutant particles such as DEP may contribute to enhanced HDM induced type 2 inflammation by expanding Ccr2-dependent monocyte-derived macrophages into the airway lumen and licensing a Th2-cytokine-responsive chemokine programme (Ccl8- Ccr8 to recruit Th2 cells; Ccl24-Ccr3 to recruit eosinophils). These findings identify luminal recruited macrophages as important targets in allergic inflammation within the lung, providing insight into potential mechanisms from which exposure and disease mitigation strategies may be developed.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}