Inhalation Toxicology最新文献

{"title":"Identification of functional roles and therapeutic targets of the STAT pathway in PM_2.5-induced allergic rhinitis.","authors":"ChiHang Zhang, JianShu Guo, Lei Lei, Lu Yu, DongXia Fan, Biao Wu, Ge Wang, WenQing Zhang, Lin Lin, XinLei Xu, XiHao Du, JinZhuo Zhao","doi":"10.1080/08958378.2025.2502791","DOIUrl":"https://doi.org/10.1080/08958378.2025.2502791","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence suggests that exposure to fine particulate matter (PM_2.5) is associated with an elevated risk of respiratory diseases. However, the precise mechanisms by which PM_2.5 influences inflammatory processes in allergic rhinitis (AR) remain insufficiently understood. The STAT pathway has been identified as a critical mediator of immune and inflammatory responses, but its specific role in modulating PM_2.5-induced effects in the nasal mucosa of AR remains unclear. This study aims to investigate the impact of PM_2.5 on the STAT pathway in the inflammatory response of the nasal mucosa during AR.</p><p><strong>Methods: </strong>We analyzed mRNA expression profiles (GSE215411) from the Gene Expression Omnibus (GEO) database to investigate the effects of PM_2.5 on human nasal mucosa-derived fibroblasts. Differential expression analysis identified differential expression genes (DEGs), which were visualized through hierarchical clustering and radar plots. GO/KEGG enrichment and Gene Set Enrichment Analysis (GSEA) identified key pathways, focusing on STAT pathway enrichment. Protein-protein interactions (PPIs) within the STAT pathway were analyzed using STRING and Cytoscapedatabase, revealing immune response and cytokine signaling as predominant functional pathways. An AR model, induced by ovalbumin sensitization and whole-body ambient PM_2.5 exposure, was utilized to assess the activation of the STAT pathway in nasal mucosal tissue.</p><p><strong>Results: </strong>A total of 426 DEGs were identified in human nasal mucosa-derived fibroblasts following PM_2.5 exposure, emphasizing STAT pathway involvement. Validation in an AR mouse model confirmed that allergens and PM_2.5 activate the STAT pathway, modulating Th2 and inflammatory cytokines.</p><p><strong>Conclusion: </strong>PM_2.5 exposure significantly activates the STAT pathway in the nasal mucosa of AR, amplifying Th2-related inflammatory cytokine response.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-16"},"PeriodicalIF":2.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150380","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":"TMEM175 activity in BK-deficient macrophages maintains lysosomal function and mediates silica-induced inflammatory response in macrophages.","authors":"Rebekah L Kendall, Britten Postma, Andrij Holian","doi":"10.1080/08958378.2025.2507251","DOIUrl":"https://doi.org/10.1080/08958378.2025.2507251","url":null,"abstract":"<p><p><b>Objective:</b> Lysosomal ion channel function in macrophages contributes to the development of silica-induced inflammation. Recent studies have shown that blocking K⁺ entry into the lysosome <i>via</i> the BK channel reduces silica-induced damage and inflammation in macrophages. This study aims to explore the mechanisms of particle-induced inflammation in BK^-/- macrophages. <b>Methods:</b> Bone marrow derived macrophages (BMdM) from C57BL/6 wildtype (WT) and BK^-/- mice were exposed <i>in vitro</i> to silica and IL-1β release and cell death assessed. The effect of BK^-/- on lysosomal pH, proteolytic activity, and cholesterol accumulation was evaluated. <b>Results:</b> BK^-/- BMdM failed to demonstrate a reduction in IL-1β or cell death following silica exposure. BK^-/- BMdM had comparable lysosome function to WT suggesting a compensatory mechanism was maintaining lysosome function. BK^-/- macrophages demonstrated an upregulation of a second lysosomal potassium channel, TMEM175. Inhibition of TMEM175 activity caused an increase in lysosomal pH and reduced silica-induced cell death and IL-1β release in both BK^-/- and WT BMdM. <b>Conclusion:</b> BK^-/- BMdM did not exhibit the same phenotype seen with pharmaceutical abrogation of BK channel activity and showed no differences from WT in response to silica exposure. Upregulation of TMEM175 in BK^-/- macrophages appears to prevent changes in lysosomal pH and cholesterol accumulation. Inhibiting TMEM175 activity in both BK^-/- and WT BMdM resulted in an increase in lysosomal pH and reduced silica-induced inflammation, suggesting that reduced particle-induced cell damage and inflammation is not dependent on the activity of a single lysosomal ion channel but rather on mechanisms that elevate lysosomal pH.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119645","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":"Beyond the puff: health consequences of vaping.","authors":"Maureen Meister, Xiaojia He, Alexandra Noël, Jin-Ah Park, Laura Crotty Alexander, Judith Zelikoff, David Christiani, Joseph Hess, Jonathan Shannahan, Christa Wright","doi":"10.1080/08958378.2025.2500646","DOIUrl":"https://doi.org/10.1080/08958378.2025.2500646","url":null,"abstract":"<p><p>Electronic nicotine delivery systems (ENDS) arrived on the U.S. market in 2007 and rapidly grew in popularity as a harm reduction tool for traditional cigarette users. While initially marketed as a healthier alternative to combustible cigarettes, the unique mixture of chemical constituents in ENDS products and their emissions have led to rising concern about their safety and the long-term health implications. Given the lack of long-term, epidemiological research on the health effects of these products, recent research has sought to understand the impacts on cellular components and gain understanding of acute effects to inform potential chronic health implications. Studies have demonstrated the deleterious effects the use of ENDS has on the oral cavity, respiratory, and cardiovascular systems. ENDS use has been linked to gingival inflammation and alterations in the oral microbiome contributing to periodontal disease. Further, the presence of heavy metals and other constituents in ENDS emissions contribute to aberrant oxidative stress and inflammation within the lung, contributing to alterations in functional lung capacity and respiratory symptoms in ENDS users. In addition, harmful components of ENDS emissions make their way to the circulatory system, leading to detrimental impacts in cardiovascular functioning such as a rise in blood pressure, impaired vascular functioning, and increased heart rate, all of which are known to underscore long-term cardiovascular ailments. This review will provide an in-depth discussion of the current literature available on the consequences of ENDS use on the oral cavity, respiratory, and cardiovascular systems as well as provide insight into long-term implications that may result.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077758","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 association between smoking profile, leukocyte count, and inflammatory indices in males: a cross-sectional analysis of the TABARI cohort study at enrollment phase.","authors":"Erfan Ghadirzadeh, Mahmood Moosazadeh, Motahareh Kheradmand, Masoumeh Bagheri-Nesami, Sajad Ghafari-Cherati, Mobina Gheibi, Amirsaeed Hosseini","doi":"10.1080/08958378.2025.2499825","DOIUrl":"https://doi.org/10.1080/08958378.2025.2499825","url":null,"abstract":"<p><strong>Background: </strong>Cigarette smoking stands as a prominent contributor to global mortality rates, and its impact spans both immediate and long-term effects on hematological parameters; however, in addition to controversial results in previous studies, its effect on novel inflammatory indices has yet to be thoroughly investigated. Thus, this study aims to assess the impact of various smoking profiles on total white blood cell (WBC) count, WBC differentials, and novel hematologic-inflammatory indices among males.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on 4039 male adults from the enrollment phase data of the TABARI cohort population in Iran. WBC, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), platelet-to-HDL ratio (PHR), RDW-to-platelet ratio (RPR), lymphocyte-to-HDL ratio (LHR), monocyte-to-HDL ratio (MHR), and neutrophil-to-HDL ratio (NHR) were compared between smokers and nonsmokers and also within smokers with different smoking intensities (pack/year). Comparisons were made by Chi-square test and one-way ANOVA, and further done using multivariate linear regression after adjustment for confounders.</p><p><strong>Results: </strong>WBC, ANC, ALC, AMC, LMR, PLR, PHR, LHR, MHR, and NHR were significantly higher in smokers compared to nonsmokers in a dose-dependent manner (<i>p</i> < 0.05). The multivariate linear regression showed that among smokers, WBC was 25.3% higher, ANC and ALC were 19.7% higher, and AMC was 12.2% higher compared to nonsmokers (all <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Our results demonstrated that WBC, ANC, ALC, AMC, PHR, LHR, MHR, and NHR exhibit significant dose-dependent elevations in smokers.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003121","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":"Association of Glutathione S-transferase gene polymorphism with coronary artery disease (CAD) in North Indian population (Jammu and Kashmir): evidence from a case-control study and an updated meta-analysis.","authors":"Jyotdeep K Raina, Ravi Sharma, Naveen Kumar, Sheikh Abid Ali, Rakesh K Panjaliya, Ashok Bakaya, Parvinder Kumar","doi":"10.1080/08958378.2025.2495592","DOIUrl":"https://doi.org/10.1080/08958378.2025.2495592","url":null,"abstract":"<p><strong>Background: </strong>Chemicals released during cigarette smoking disrupt the structure, function and physiological capacity of the cardiovascular system. Detoxification of these harmful chemicals is done by Glutathione S-transferase (GST) isoenzymes (GSTM1 and GSTT1). GST gene polymorphisms may have a role in conferring susceptibility to coronary artery disease. This case-control study aims to evaluate the relationship between GSTM1 and GSTT1 gene polymorphisms, smoking habits, and coronary artery disease (CAD) in the Northern Indian population of Jammu and Kashmir, strengthened by a meta-analysis based on previously published studies.</p><p><strong>Methods: </strong>The current study involved 220 patients with CAD and 240 healthy controls from the Jammu region in the Union Territory of Jammu and Kashmir. Whole blood DNA was isolated, followed by genotyping using the polymerase chain reaction (PCR) technique.</p><p><strong>Results: </strong>Smoking, a non-vegetarian diet, and lipid levels were found to be significantly associated with coronary artery disease (CAD). The frequency of the GSTM^null genotype was significantly higher in patients than in controls (48.2% vs. 33.3%), while both groups showed comparable frequencies of the GSTT^null genotype. Combined genotype analysis indicated that the GSTM1 T^null genotype was associated with an increased risk of CAD, with an adjusted odds ratio (AOR) of 1.70 and a 95% confidence interval (CI) of 1.30-2.27(<i>p</i> = 0.05). Patients who were smokers and had the GSTM^null genotype, as well as those with the GSTM1T^null or GSTM^nullT1 genotypes, were at a significantly higher risk of developing CAD. The results of the meta-analysis supported the findings of the case-control association study.</p><p><strong>Conclusion: </strong>The GSTM1 null genotype, either independently or in conjunction with smoking, is linked to the incidence of CAD among North Indians in Jammu and Kashmir.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986071","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 empirical metric of mesothelial carcinogenicity for carbon nanotubes and elongate mineral particles.","authors":"Andrey A Korchevskiy, Ann G Wylie","doi":"10.1080/08958378.2025.2486087","DOIUrl":"https://doi.org/10.1080/08958378.2025.2486087","url":null,"abstract":"<p><strong>Introduction: </strong>Carcinogenic potential of elongate particles depends on many characteristics, with dimensional parameters playing an important role at all stages of disease origination and progression. It is important to develop quantitative metrics of mesothelial carcinogenicity for particles in order to predict their behavior within biological systems. It would be especially valuable if such metrics could be developed for both carbon nanotubes (CNTs) and elongate mineral particles (EMPs) to demonstrate similarities and differences in the estimations of mesothelioma risk.</p><p><strong>Methods: </strong>The database is organized with dimensional characteristics of EMPs, containing 570,950 records for 246 asbestiform, non-asbestiform, and mixed datasets. A database on carbon nanotubes (CNTs) with various toxicological outcomes of animal experiments, including mesothelioma, was also created. Mathematical modeling was used to determine the best metric of mesotheliomagenicity that would work for CNTs and EMPs.</p><p><strong>Results: </strong>The dimensional coefficient of carcinogenicity (DCC) was introduced with the formula DCC = 1-exp(-AxSA/(BxWidth³+C)), where SA - surface area of the elongate particle, Width - particle width, A, B, C - coefficients. It was demonstrated that DCC can efficiently determine mesotheliomagenic varieties of CNTs and EMPs, with a threshold for carcinogenic potential of 0.05 with <i>A</i> = 0.11, <i>B</i> = 1000, <i>C</i> = 1.</p><p><strong>Discussion: </strong>The new quantitative metric of carcinogenicity can be used for the purposes of mineralogical evaluation and toxicological analysis. It was confirmed that DCC-based models predict negligible mesothelioma potency for non-asbestiform amphiboles.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-26"},"PeriodicalIF":2.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982031","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":"Deconstructing ENDS aerosols: generation and characterization methods.","authors":"Shaligram Sharma, Maureen Meister, David Christiani, Qian Zhang, Mark Wilson, Travis Goldsmith, I Mark Olfert, Anand Ranpara, Cristi Bell-Huff, Marilyn Black, Jonathan Shannahan, Christa Wright","doi":"10.1080/08958378.2025.2481434","DOIUrl":"https://doi.org/10.1080/08958378.2025.2481434","url":null,"abstract":"<p><p>While electronic nicotine delivery systems or ENDS are often marketed as a safer alternative to traditional cigarettes, emissions generated during the operation of these devices contain a complex mixture of toxic substances. ENDS emissions are primarily composed of fine particulate matter (PM_2.5, smaller than 2.5 µm in size) and ultrafine particles/nanoparticles (PM_0.1, smaller than 100 nm in size), metals (nickel, copper, zinc, tin, lead, and their oxides), carbonyls (formaldehyde, acetaldehyde (a carcinogen), and acrolein), volatile organic compounds (VOCs) (benzene, toluene, and over 70 other VOCs), nicotine, and many unknown chemicals. The levels and composition of these toxic emissions can vary based on factors like device design, e-liquid formulation, device power and temperature levels, and vaping behavior of the user. Within this section of the Special Issue 'Science Education and Research on Vaping and Interventions for Community Engagement', important parameters in defining and characterizing ENDS aerosols will be discussed. Hazardous components of ENDS aerosols including particulate matter, heavy metals, and volatile organic compounds will be delineated and appropriate analytical methods to accurately determine physicochemical properties will be highlighted. Definitions and comparisons of first-hand, second-hand, and third-hand emissions will also be explored alongside pertinent device parameters that influence each type of ENDS emission.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730090","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 beginning of ENDS (electronic nicotine delivery systems): origins, trends, and regulatory considerations.","authors":"Shaligram Sharma, Maureen Meister, Scott Weaver, Judith Zelikoff, Cristi Bell-Huff, Marilyn Black, Jonathan Shannahan, Christa Wright","doi":"10.1080/08958378.2025.2479518","DOIUrl":"https://doi.org/10.1080/08958378.2025.2479518","url":null,"abstract":"<p><p>Electronic nicotine delivery systems (ENDS), commonly known as e-cigarettes, are battery-operated devices that produce aerosols by vaporizing e-liquids, which typically contain propylene glycol and/or vegetable glycerin, nicotine, and flavorings. Since their launch in the U.S. in 2007, ENDS have evolved significantly to meet consumer demands, prompting federal regulation in 2016 under the Family Smoking Prevention and Tobacco Control Act. The first ENDS resembled conventional tobacco cigarettes and were initially marketed as smoking cessation tools. While their smoking cessation efficacy under advantageous conditions has been supported by randomized clinical trials, observational cohort studies have raised doubt about their utility for smoking cessation under more typical real-world use conditions. In 2018, the U.S. Surgeon General declared youth vaping a national epidemic as prevalence of current ENDS use rose to 27.5% among high school. The youth vaping trend alongside injury reports and deaths related to e-cigarette or vaping product use-associated lung injury (EVALI) raised public health alarms in 2019. Although youth vaping has since declined, over 1.6 million high school students and 410, 000 middle school students reported ENDS usage in 2024. Thus, the ongoing challenges surrounding vaping including adolescent usage and smoking cessation efficacy continue to attract public health concern and debate. Within this section of the Special Issue \"Science Education and Research on Vaping and Interventions for Community Engagement\", an overview of the history of the vaping epidemic, current formats and ENDS generations, usage statistics across various demographics along with market trends and regulatory guidelines will be discussed.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":2.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718660","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":"CARD9 deficiency alleviates septic pulmonary embolism.","authors":"Zhaoli Zhang, Lingyun Zhu, Yunji Wang, Wantong Tian, Hui Li","doi":"10.1080/08958378.2025.2473432","DOIUrl":"10.1080/08958378.2025.2473432","url":null,"abstract":"<p><p><b>Purpose:</b> Dysfunction of pulmonary microvascular endothelial cells (PMVECs) is an important feature of pulmonary embolism (PE) in sepsis. This study aimed to explore the impact of caspase recruitment domain-containing protein 9 (CARD9) on sepsis-induced PE. <b>Materials and Methods:</b> Proteomic analysis was performed on serum of sepsis patients with PE to identify differentially expressed proteins. Wild-type (WT) and CARD9 knockout (KO) mice were used to establish PE in sepsis mouse model. In vitro and in vivo sepsis models were established to evaluate PMVEC function. Tiliroside (TIS) was tested for its therapeutic effects via modulation of the CARD9-mediated MAPK/NF-κB pathway. <b>Results:</b> In the pulmonary vascular endothelial tissues of mice with sepsis, a total of 46 proteins exhibited differential expression, and CARD9 was one of the changes proteins. Both CARD9 knockout (KO) and silencing were found to effectively ameliorate sepsis-induced dysfunction of PMVECs in both in vivo and in vitro models of sepsis. Tiliroside (TIS), an active constituent derived from Buddleja officinalis Maxim, demonstrated a significant capacity to enhance the function of PMVECs in sepsis by modulating the CARD9-mediated MAPK/NF-κB signaling pathway. <b>Conclusion:</b> In summary, CARD9 emerges as a potential molecular target for the treatment of sepsis-associated PE dysfunction.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"87-97"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752510","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":"A mechanistic review-regulation of silica-induced pulmonary inflammation by IL-10 and exacerbation by Type I IFN.","authors":"Hajime Kawasaki","doi":"10.1080/08958378.2025.2465378","DOIUrl":"10.1080/08958378.2025.2465378","url":null,"abstract":"<p><p>Occupational exposure to crystalline silica (CS) is known to induce silicosis, a chronic lung disease characterized by the formation of granulomas and severe lung fibrosis. Specifically, individuals exposed to low doses of CS may develop silicosis after a decade or more of exposure. Similarly, in rat silicosis models exposed to occupationally relevant doses of α-quartz, there is an initial phase characterized by minimal and well-controlled pulmonary inflammation, followed by the development of robust and persistent inflammation. During the initial phase, the inflammation provoked by α-quartz is subdued by two mechanisms. Firstly, α-quartz particles are engulfed by alveolar macrophages (AMs) of the alternatively activated (M2) subtype and interstitial macrophages (IMs), limiting their interaction with other lung cells. Secondly, the anti-inflammatory cytokine, interleukin (IL)-10, is constitutively expressed by these macrophages, further dampening the inflammatory response. In the later inflammatory phase, IL-10-dependent anti-inflammatory state is disrupted by Type I interferons (IFNs), leading to the production of pro-inflammatory cytokines in response to α-quartz, aided by lipopolysaccharides (LPS). This review delves into the complex pathways involving IL-10, LPS, and Type I IFNs in α-quartz-induced pulmonary inflammation, offering a detailed analysis of the underlying mechanisms and identifying areas for future research.</p>","PeriodicalId":13561,"journal":{"name":"Inhalation Toxicology","volume":" ","pages":"59-73"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425298","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}