Toxicological Sciences最新文献_第10页

Quantitative cross-species comparison of serum albumin binding of per- and polyfluoroalkyl substances from five structural classes. 五种结构类别的全氟烷基和多氟烷基物质与血清白蛋白结合的跨物种定量比较。

IF 3.4 3区医学

Toxicological Sciences Pub Date : 2024-04-29 DOI: 10.1093/toxsci/kfae028

Hannah M Starnes, Thomas W Jackson, Kylie D Rock, Scott M Belcher

{"title":"Quantitative cross-species comparison of serum albumin binding of per- and polyfluoroalkyl substances from five structural classes.","authors":"Hannah M Starnes, Thomas W Jackson, Kylie D Rock, Scott M Belcher","doi":"10.1093/toxsci/kfae028","DOIUrl":"10.1093/toxsci/kfae028","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are a class of over 8000 chemicals, many of which are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput, in vitro differential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and the perfluoroalkyl ether acid congener bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model, and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive bioaccumulation and toxicity assessments for PFAS.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"132-149"},"PeriodicalIF":3.4,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug-induced impairment of mitochondrial fatty acid oxidation and steatosis: assessment of causal relationship with 45 pharmaceuticals 药物诱导的线粒体脂肪酸氧化和脂肪变性损伤：评估与 45 种药物的因果关系

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-27 DOI: 10.1093/toxsci/kfae055

Nelly Buron, Mathieu Porceddu, Roxane Loyant, Cécile Martel, Julien A Allard, Bernard Fromenty, Annie Borgne-Sanchez

{"title":"Drug-induced impairment of mitochondrial fatty acid oxidation and steatosis: assessment of causal relationship with 45 pharmaceuticals","authors":"Nelly Buron, Mathieu Porceddu, Roxane Loyant, Cécile Martel, Julien A Allard, Bernard Fromenty, Annie Borgne-Sanchez","doi":"10.1093/toxsci/kfae055","DOIUrl":"https://doi.org/10.1093/toxsci/kfae055","url":null,"abstract":"Drug-induced liver injury (DILI) represents a major issue for pharmaceutical companies, being a potential cause of black-box warnings on marketed pharmaceuticals, or drug withdrawal from the market. Lipid accumulation in the liver also referred to as steatosis, may be secondary to impaired mitochondrial fatty acid oxidation (mtFAO). However, an overall causal relationship between drug-induced mtFAO inhibition and the occurrence of steatosis in patients has not yet been established with a high number of pharmaceuticals. Hence, 32 steatogenic and 13 non-steatogenic drugs were tested for their ability to inhibit mtFAO in isolated mouse liver mitochondria. To this end, mitochondrial respiration was measured with palmitoyl-L-carnitine, palmitoyl-CoA + L-carnitine, or octanoyl-L-carnitine. This mtFAO tri-parametric assay was able to predict the occurrence of steatosis in patients with a sensitivity and positive predictive value above 88%. To get further information regarding the mechanism of drug-induced mtFAO impairment, mitochondrial respiration was also measured with malate/glutamate or succinate. Drugs such as diclofenac, methotrexate and troglitazone could inhibit mtFAO secondary to an impairment of the mitochondrial respiratory chain, while dexamethasone, olanzapine and zidovudine appeared to impair mtFAO directly. Mitochondrial swelling, transmembrane potential and production of reactive oxygen species were also assessed for all compounds. Only the steatogenic drugs amiodarone, ketoconazole, lovastatin and toremifene altered all these 3 mitochondrial parameters. In conclusion, our tri-parametric mtFAO assay could be useful in predicting the occurrence of steatosis in patients. The combination of this assay with other mitochondrial parameters could also help to better understand the mechanism of drug-induced mtFAO inhibition.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"131 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: An analysis of the data from Toxicity Reference Database (ToxRefDB) 化学品暴露对小鼠和大鼠造成的组织病理学影响与肝脏重量变化之间的关联：毒性参考数据库（ToxRefDB）数据分析

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-23 DOI: 10.1093/toxsci/kfae056

R Mezencev, M Feshuk, L Kolaczkowski, G C Peterson, Q J Zhao, S Watford, J A Weaver

引用次数: 0

Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood 单细胞转录组学揭示了早期 BDE-99 暴露对肠道-肝脏轴的重编程作用，从而促进雄性小鼠成年晚期的促炎症代谢特征

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-18 DOI: 10.1093/toxsci/kfae047

Joe Jongpyo Lim, Michael Goedken, Yan Jin, Haiwei Gu, Julia Yue Cui

{"title":"Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood","authors":"Joe Jongpyo Lim, Michael Goedken, Yan Jin, Haiwei Gu, Julia Yue Cui","doi":"10.1093/toxsci/kfae047","DOIUrl":"https://doi.org/10.1093/toxsci/kfae047","url":null,"abstract":"Polybrominated diphenyl ethers (PBDEs) are legacy flame retardants that bioaccumulate in the environment. The gut microbiome is an important regulator of liver functions including xenobiotic biotransformation and immune regulation. We recently showed that neonatal exposure to polybrominated diphenyl ether-99 (BDE-99), a human breast milk-enriched PBDE congener, up-regulated pro-inflammation- and down-regulated drug metabolism-related genes predominantly in males in young adulthood. However, the persistence of dysregulation into late adulthood, differential impact of hepatic cell types, and the involvement of the gut microbiome from neonatal BDE-99 exposure remains unknown. To address these knowledge gaps, male C57BL/6 mouse pups were orally exposed to corn oil (10 ml/kg) or BDE-99 (57 mg/kg) once daily from postnatal days 2-4. At 15 months of age, neonatal BDE-99 exposure down-regulated xenobiotic and lipid metabolizing enzymes and up-regulated genes involved in microbial influx in hepatocytes. Neonatal BDE-99 exposure also increased the hepatic proportion of neutrophils and led to a predicted increase of macrophage migration inhibitory factor signaling. This was associated with decreased intestinal tight junction protein (Tjp) transcripts, altered gut environment, and dysregulation of inflammation-related metabolites. ScRNA-seq using germ-free (GF) mice demonstrated the necessity of a normal gut microbiome in maintaining hepatic immune tolerance. Microbiota transplant to GF mice using large intestinal microbiome from adults neonatally exposed to BDE-99 down-regulated Tjp transcripts and up-regulated several cytokines in the large intestine. In conclusion, neonatal BDE-99 exposure reprogrammed cell type-specific gene expression and communication in liver towards pro-inflammation, and BDE-99-mediated pro-inflammatory signatures may be partly due to the dysregulated gut environment.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"100 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parameter grouping and Co-estimation in Physiologically-Based kinetic models using genetic algorithms 利用遗传算法对基于生理学的动力学模型进行参数分组和共同估计

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-18 DOI: 10.1093/toxsci/kfae051

Periklis Tsiros, Vasileios Minadakis, Dingsheng Li, Haralambos Sarimveis

{"title":"Parameter grouping and Co-estimation in Physiologically-Based kinetic models using genetic algorithms","authors":"Periklis Tsiros, Vasileios Minadakis, Dingsheng Li, Haralambos Sarimveis","doi":"10.1093/toxsci/kfae051","DOIUrl":"https://doi.org/10.1093/toxsci/kfae051","url":null,"abstract":"Physiologically-based kinetic (PBK) models are widely used in pharmacology and toxicology for predicting the internal disposition of substances upon exposure, voluntarily or not. Due to their complexity, a large number of model parameters need to be estimated, either through in silico tools, in vitro experiments or by fitting the model to in vivo data. In the latter case, fitting complex structural models on in vivo data can result in overparameterisation and produce unrealistic parameter estimates. To address these issues, we propose a novel parameter grouping approach, which reduces the parametric space by co-estimating groups of parameters across compartments. Grouping of parameters is performed using genetic algorithms and is fully automated, based on a novel goodness-of-fit metric. To illustrate the practical application of the proposed methodology, two case studies were conducted. The first case study demonstrates the development of a new PBK model, while the second focuses on model refinement. In the first case study, a PBK model was developed to elucidate the biodistribution of titanium dioxide (TiO2) nanoparticles in rats following intravenous injection. A variety of parameter estimation schemes were employed. Comparative analysis based on goodness-of-fit metrics demonstrated that the proposed methodology yields models that outperform standard estimation approaches, while utilising a reduced number of parameters. In the second case study, an existing PBK model for perfluorooctanoic acid (PFOA) in rats was extended to incorporate additional tissues, providing a more a comprehensive portrayal of PFOA biodistribution. Both models were validated through independent in vivo studies to ensure their reliability.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"20 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miRNAs mediate impact of smoking on dental pulp stem cells via p53 pathway miRNA 通过 p53 通路介导吸烟对牙髓干细胞的影响

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-18 DOI: 10.1093/toxsci/kfae042

Leyla Tahrani Hardin, Nabil Abid, David Vang, Xiaoyuan Han, Der Thor, David M Ojcius, Nan Xiao

{"title":"miRNAs mediate impact of smoking on dental pulp stem cells via p53 pathway","authors":"Leyla Tahrani Hardin, Nabil Abid, David Vang, Xiaoyuan Han, Der Thor, David M Ojcius, Nan Xiao","doi":"10.1093/toxsci/kfae042","DOIUrl":"https://doi.org/10.1093/toxsci/kfae042","url":null,"abstract":"Cigarette smoke changes the genomic and epigenomic imprint of cells. In this study, we investigated the biological consequences of extended cigarette smoke exposure on dental pulp stem cells (DPSCs) and the potential roles of miRNAs. DPSCs were treated with various doses of cigarette smoke condensate (CSC) for up to six weeks. Cell proliferation, survival, migration, and differentiation were evaluated. Cytokine and miRNA expression were profiled. The results showed that extended exposure to CSC significantly impaired the regenerative capacity of the DPSCs. Bioinformatic analysis showed that the cell cycle pathway, cancer pathways (small cell lung cancer, pancreatic, colorectal, and prostate cancer), and pathways for TNF, TGF-β, p53, PI3K-Akt, mTOR and ErbB signal transduction, were associated with altered miRNA profiles. In particular, three miRNAs has-miR-26a-5p, has-miR-26b-5p and has-miR-29b-3p fine tune the p53 and cell cycle signaling pathways to regulate DPSC cellular activities. The work indicated that miRNAs are promising targets to modulate stem cell regeneration and understanding miRNA-targeted genes and their associated pathways in smoking individuals have significant implications for disease control and prevention.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"124 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of corticosterone in nevirapine-induced idiosyncratic drug-induced liver injury 皮质酮在奈韦拉平引起的特异性药物性肝损伤中的作用

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-17 DOI: 10.1093/toxsci/kfae054

Alison Jee, Samantha Christine Sernoskie, Jack Uetrecht

{"title":"The role of corticosterone in nevirapine-induced idiosyncratic drug-induced liver injury","authors":"Alison Jee, Samantha Christine Sernoskie, Jack Uetrecht","doi":"10.1093/toxsci/kfae054","DOIUrl":"https://doi.org/10.1093/toxsci/kfae054","url":null,"abstract":"Nevirapine, an antiretroviral used in the treatment of HIV, is associated with idiosyncratic drug-induced liver injury (IDILI), a potentially life-threatening adverse drug reaction. Its usage has decreased due to this concern, but it is still widely used in lower-resource settings. In general, the mechanisms underlying idiosyncratic drug reactions (IDRs) are poorly understood, but evidence indicates that most are immune-mediated. There is very limited understanding of the early immune response following administration of drugs associated with IDRs, which likely occurs due to reactive metabolite formation. In this work, we aimed to characterize the links between covalent binding of nevirapine, the development of an early immune response, and the subsequent liver injury using a mouse model. We describe initial attempts to characterize an early immune response to nevirapine followed by the discovery that nevirapine induced the release of corticosterone. Corticosterone release was partially associated with the degree of drug covalent binding in the liver but was also likely mediated by additional mechanisms at higher drug doses. Transcriptomic analysis confirmed metabolic activation, glucocorticoid signaling, and decreased immune activation; GDF-15 also warrants further investigation as part of the immune response to nevirapine. Finally, glucocorticoid blockade preceding the first dose of nevirapine attenuated nevirapine-induced liver injury at 3 weeks, suggesting that acute glucocorticoid signaling is harmful in the context of nevirapine-induced liver injury. This work demonstrates that nevirapine induces acute corticosterone release, which contributes to delayed-onset liver injury. It also has implications for screening drug candidates for IDILI risk and preventing nevirapine-induced IDILI.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"44 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An environmentally relevant mixture of Perfluoroalkyl Substances (PFAS) impacts proliferation, steroid hormone synthesis, and gene transcription in primary human granulosa cells 与环境相关的全氟烷基物质（PFAS）混合物影响原代人类颗粒细胞的增殖、类固醇激素合成和基因转录

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-11 DOI: 10.1093/toxsci/kfae049

Kendra L Clark, Mamta Shukla, Jitu W George, Stephanie Gustin, M Jordan Rowley, John S Davis

{"title":"An environmentally relevant mixture of Perfluoroalkyl Substances (PFAS) impacts proliferation, steroid hormone synthesis, and gene transcription in primary human granulosa cells","authors":"Kendra L Clark, Mamta Shukla, Jitu W George, Stephanie Gustin, M Jordan Rowley, John S Davis","doi":"10.1093/toxsci/kfae049","DOIUrl":"https://doi.org/10.1093/toxsci/kfae049","url":null,"abstract":"Perfluoroalkyl substances (PFAS) are a group of synthetic chemicals that are resistant to biodegradation and are environmentally persistent. PFAS are found in many consumer products and are a major source of water and soil contamination. This study investigated the effects of an environmentally relevant PFAS mixture [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS)] on the transcriptome and function of human granulosa cells (hGCs). Primary hGCs were harvested from follicular aspirates of healthy, reproductive-age women who were undergoing oocyte retrieval for in vitro fertilization. LC/MS-MS was performed to identify PFAS compounds in pure follicular fluid. Cells were cultured with vehicle control or a PFAS mixture (2 nM PFHxS, 7 nM PFOA, 10 nM PFOS) for 96h. Analyses of cell proliferation/apoptosis, steroidogenesis, and gene expression were measured via MTT assays/immunofluorescence, ELISA/western blotting, and RNA sequencing/bioinformatics, respectively. PFOA, PFOS, and PFHxS were detected in 100% of follicle fluid samples. Increased cell proliferation was observed in hGCs treated with the PFAS mixture with no impacts on cellular apoptosis. The PFAS mixture also altered steroid hormone synthesis, increasing both FSH-stimulated and basal progesterone secretion and concomitant upregulation of STAR protein. RNA sequencing revealed inherent differences in transcriptomic profiles in hGCs after PFAS exposure. This study demonstrates functional and transcriptomic changes in hGCs after exposure to a PFAS mixture, improving our knowledge about the impacts of PFAS exposures and female reproductive health. These findings suggest that PFAS compounds can disrupt normal granulosa cell function with possible long-term consequences on overall reproductive health.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"36 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels nor blood coagulation 胆色素短期治疗可提高兔子体内长效抗凝血杀鼠剂的清除率，但不会影响血浆维生素 K1 水平或血液凝固过程

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-11 DOI: 10.1093/toxsci/kfae053

Ruth N Muchiri, Jackie Rocha, Ankit Tandon, Yongmei Luo Chen, Rebecca Alemani, Intakhar Ahmad, Zachary McDonald, Matthew Lindeblad, Israel Rubinstein, Richard B van Breemen, Douglas L Feinstein

{"title":"Short-term treatment with cholestyramine increases long-acting anticoagulant rodenticide clearance from rabbits without affecting plasma vitamin K1 levels nor blood coagulation","authors":"Ruth N Muchiri, Jackie Rocha, Ankit Tandon, Yongmei Luo Chen, Rebecca Alemani, Intakhar Ahmad, Zachary McDonald, Matthew Lindeblad, Israel Rubinstein, Richard B van Breemen, Douglas L Feinstein","doi":"10.1093/toxsci/kfae053","DOIUrl":"https://doi.org/10.1093/toxsci/kfae053","url":null,"abstract":"Administration of high dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anti-coagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, nor increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anti-coagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms underlying aryl hydrocarbon receptor-driven divergent macrophage function 芳基烃受体驱动巨噬细胞功能分化的机制

IF 3.8 3区医学

Toxicological Sciences Pub Date : 2024-04-11 DOI: 10.1093/toxsci/kfae050

Keegan Malany, Xiaohan Li, Christoph F A Vogel, Allison K Ehrlich

{"title":"Mechanisms underlying aryl hydrocarbon receptor-driven divergent macrophage function","authors":"Keegan Malany, Xiaohan Li, Christoph F A Vogel, Allison K Ehrlich","doi":"10.1093/toxsci/kfae050","DOIUrl":"https://doi.org/10.1093/toxsci/kfae050","url":null,"abstract":"Macrophages play an essential role in the innate immune system by differentiating into functionally diverse subsets in order to fight infection, repair damaged tissues, and regulate inappropriate immune responses. This functional diversity stems from their ability to adapt and respond to signals in the environment, which is in part mediated through aryl hydrocarbon receptor (AHR)-signaling. AHR, an environmental sensor, can be activated by various ligands, ranging from environmental contaminants to microbially derived tryptophan metabolites. This review discusses what is currently known about how AHR-signaling influences macrophage differentiation, polarization, and function. By discussing studies that are both consistent and divergent, our goal is to highlight the need for future research on the mechanisms by which AHR acts as an immunological switch in macrophages. Ultimately, understanding the contexts in which AHR-signaling promotes and/or inhibits differentiation, proinflammatory functions, and immunoregulatory functions, will help uncover functional predictions of immunotoxicity following exposure to environmental chemicals as well as better design AHR-targeted immunotherapies.","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":"35 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0