{"title":"膳食中黄曲霉毒素 G1 的暴露会导致母鼠和子鼠肺组织驻留的肺泡巨噬细胞与单核细胞衍生的巨噬细胞之间的失衡","authors":"","doi":"10.1016/j.ecoenv.2024.117082","DOIUrl":null,"url":null,"abstract":"<div><div>Aflatoxin G<sub>1</sub> (AFG<sub>1</sub>) is a mycotoxin commonly found in agricultural products, including dried fruits, meat, and milk products. Oral AFG<sub>1</sub> administration induced tumor necrosis factor (TNF)-α-dependent chronic pulmonary inflammation, promoting AFG<sub>1</sub>-induced damage in alveolar epithelial cell, which is associated with lung adenocarcinoma. Pulmonary macrophages may be divided into tissue-resident alveolar macrophages (TRAMs) and monocyte-derived macrophages (MoMs), which involve in chronic lung inflammation. However, whether these macrophages contribute to AFG<sub>1</sub>-induced chronic pulmonary inflammation remains unknown. In this study, we found oral AFG<sub>1</sub> administration disrupted the balance between TRAMs and MoMs, increasing MoMs infiltration and decreasing the number of TRAMs. AFG<sub>1</sub> upregulated TNF-α expression in MoMs, but downregulated sialic acid binding Ig-like lectin F (Siglec-F) expression in TRAMs. Inhibition of TNF-α-dependent inflammation rescued the imbalance between TRAMs and MoMs in AFG<sub>1</sub>-treated lung tissues. Additionally, AFG<sub>1</sub> stimulated MoMs differentiation to the proinflammatory M1 phenotype <em>in vitro.</em> Using a specific in vitro TRAM model, AFG<sub>1</sub> downregulated Siglec-F and the M2 phenotypic markers arginase 1 and YM1, and upregulated the M1 phenotypic markers IL-6, iNOS and TNF-α, altering the TRAMs phenotype to the pro-inflammatory M1 phenotype <em>in vitro</em>. Additionally, mouse maternal dietary exposure to AFG<sub>1</sub> caused an imbalance in pulmonary macrophages, decreasing TRAMs and increasing MoMs population in offspring, which was associated with proliferative lesions in the alveolar septa. Thus, dietary AFG<sub>1</sub> exposure triggered an imbalance in pulmonary macrophages in both mother and offspring mice, and induced pro-inflammatory phenotypic alterations, which contributed to AFG<sub>1</sub>-induced chronic lung inflammation. These results provide clues to how AFG<sub>1</sub>-induced immunotoxicity and genotoxicity in humans might be prevented.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0147651324011588/pdfft?md5=4af1b2bc3bc9c5e5146d858c15b4eef8&pid=1-s2.0-S0147651324011588-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Dietary Aflatoxin G1 exposure causes an imbalance between pulmonary tissue-resident alveolar macrophages and monocyte-derived macrophages in both mother and offspring mice\",\"authors\":\"\",\"doi\":\"10.1016/j.ecoenv.2024.117082\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Aflatoxin G<sub>1</sub> (AFG<sub>1</sub>) is a mycotoxin commonly found in agricultural products, including dried fruits, meat, and milk products. Oral AFG<sub>1</sub> administration induced tumor necrosis factor (TNF)-α-dependent chronic pulmonary inflammation, promoting AFG<sub>1</sub>-induced damage in alveolar epithelial cell, which is associated with lung adenocarcinoma. Pulmonary macrophages may be divided into tissue-resident alveolar macrophages (TRAMs) and monocyte-derived macrophages (MoMs), which involve in chronic lung inflammation. However, whether these macrophages contribute to AFG<sub>1</sub>-induced chronic pulmonary inflammation remains unknown. In this study, we found oral AFG<sub>1</sub> administration disrupted the balance between TRAMs and MoMs, increasing MoMs infiltration and decreasing the number of TRAMs. AFG<sub>1</sub> upregulated TNF-α expression in MoMs, but downregulated sialic acid binding Ig-like lectin F (Siglec-F) expression in TRAMs. Inhibition of TNF-α-dependent inflammation rescued the imbalance between TRAMs and MoMs in AFG<sub>1</sub>-treated lung tissues. Additionally, AFG<sub>1</sub> stimulated MoMs differentiation to the proinflammatory M1 phenotype <em>in vitro.</em> Using a specific in vitro TRAM model, AFG<sub>1</sub> downregulated Siglec-F and the M2 phenotypic markers arginase 1 and YM1, and upregulated the M1 phenotypic markers IL-6, iNOS and TNF-α, altering the TRAMs phenotype to the pro-inflammatory M1 phenotype <em>in vitro</em>. Additionally, mouse maternal dietary exposure to AFG<sub>1</sub> caused an imbalance in pulmonary macrophages, decreasing TRAMs and increasing MoMs population in offspring, which was associated with proliferative lesions in the alveolar septa. Thus, dietary AFG<sub>1</sub> exposure triggered an imbalance in pulmonary macrophages in both mother and offspring mice, and induced pro-inflammatory phenotypic alterations, which contributed to AFG<sub>1</sub>-induced chronic lung inflammation. These results provide clues to how AFG<sub>1</sub>-induced immunotoxicity and genotoxicity in humans might be prevented.</div></div>\",\"PeriodicalId\":303,\"journal\":{\"name\":\"Ecotoxicology and Environmental Safety\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0147651324011588/pdfft?md5=4af1b2bc3bc9c5e5146d858c15b4eef8&pid=1-s2.0-S0147651324011588-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ecotoxicology and Environmental Safety\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0147651324011588\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147651324011588","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Dietary Aflatoxin G1 exposure causes an imbalance between pulmonary tissue-resident alveolar macrophages and monocyte-derived macrophages in both mother and offspring mice
Aflatoxin G1 (AFG1) is a mycotoxin commonly found in agricultural products, including dried fruits, meat, and milk products. Oral AFG1 administration induced tumor necrosis factor (TNF)-α-dependent chronic pulmonary inflammation, promoting AFG1-induced damage in alveolar epithelial cell, which is associated with lung adenocarcinoma. Pulmonary macrophages may be divided into tissue-resident alveolar macrophages (TRAMs) and monocyte-derived macrophages (MoMs), which involve in chronic lung inflammation. However, whether these macrophages contribute to AFG1-induced chronic pulmonary inflammation remains unknown. In this study, we found oral AFG1 administration disrupted the balance between TRAMs and MoMs, increasing MoMs infiltration and decreasing the number of TRAMs. AFG1 upregulated TNF-α expression in MoMs, but downregulated sialic acid binding Ig-like lectin F (Siglec-F) expression in TRAMs. Inhibition of TNF-α-dependent inflammation rescued the imbalance between TRAMs and MoMs in AFG1-treated lung tissues. Additionally, AFG1 stimulated MoMs differentiation to the proinflammatory M1 phenotype in vitro. Using a specific in vitro TRAM model, AFG1 downregulated Siglec-F and the M2 phenotypic markers arginase 1 and YM1, and upregulated the M1 phenotypic markers IL-6, iNOS and TNF-α, altering the TRAMs phenotype to the pro-inflammatory M1 phenotype in vitro. Additionally, mouse maternal dietary exposure to AFG1 caused an imbalance in pulmonary macrophages, decreasing TRAMs and increasing MoMs population in offspring, which was associated with proliferative lesions in the alveolar septa. Thus, dietary AFG1 exposure triggered an imbalance in pulmonary macrophages in both mother and offspring mice, and induced pro-inflammatory phenotypic alterations, which contributed to AFG1-induced chronic lung inflammation. These results provide clues to how AFG1-induced immunotoxicity and genotoxicity in humans might be prevented.
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.