Xiangjun Fu, Jie Xu, Chengyu Ni, Degang Yu, Haibo Wang, Pan Wang, Man Luo, Jie Yu
{"title":"壬基酚亚慢性暴露对大鼠脾脏免疫相关因子及雌激素受体表达的影响","authors":"Xiangjun Fu, Jie Xu, Chengyu Ni, Degang Yu, Haibo Wang, Pan Wang, Man Luo, Jie Yu","doi":"10.1186/s12302-022-00610-6","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Previous studies have shown that EDCs may activate nuclear transcription factor, such as activator protein-1 (AP-1), nuclear factor of activated Tcells (NF-AT) and nuclear factor kappa B (NF-κB) in the process of immune damage. At the same time, some experts believed that estrogen may play an important role in this process. As a typical representative of EDCs, nonylphenol (NP) has not been reported. The aim of this work was to explore the relationship between the immune inflammatory damage and the changes in estrogen expression in male rats during the chronic exposure to NP at environmental concentrations. Sixty SPF Sprague–Dawley rats were divided into five groups (<i>n</i> = 12 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E<sub>2</sub>: 30 μg/kg/d).</p><h3>Results</h3><p>Compared with the control group, rat spleen organ coefficient, number of spleen nodules, relative area of lymph nodes and white pulp were relatively reduced in the L (NP, 0.4 mg/kg) and H (NP, 40 mg/kg) exposure dose groups (<i>P</i> < 0.001). Lymphocytes were rich in cytoplasm, mitochondria were swollen, part of the cristae was reduced, and rough endoplasmic reticulum was expanded. The serum levels of IgG (<i>P</i> < 0.001) and IgM (<i>P</i> = 0.002) showed a downward trend. The percentage of Th cells (CD3<sup>+</sup>CD4<sup>+</sup>) was significantly decreased (<i>P</i> < 0.001), and the percentage of B lymphocytes shows an opposite trend (<i>P</i> < 0.001). Giemsa staining showed that the number of neutrophils (<i>P</i> < 0.001) was increased. The expressions of estrogen receptor ER-α and ER-β protein in the spleen increased significantly (<i>P</i> < 0.001). The expressions of AP-1 protein and NF-AT protein in the spleen were increased, and the expression of NF-KB protein was decreased (<i>P</i> < 0.001). The expressions of IL-4, ER-α and ER-β (<i>P</i> < 0.001) levels in serum increased. The mRNA-seq bioinformatics detection showed the final differentially expressed immune-inflammatory-related genes between the control and H-NP groups as follow: down-regulated: TLR4, Gata3, IL12, up-regulated: TNF-a, IL10, INOS. The mRNA expressions of ER-α, ER-β, NF-KB, IL4, AP-1, TLR4, Gata3, and NF-AT were consistent with the results of mRNA-seq analysis. NP content was correlated with the expressions of ER-α, ER-β, IL4, AP-1, NF-AT, TLR4, NF-KB, as well as IL-12 proteins in the spleen tissue ([<i>r</i>] < 1, <i>P</i> < 0.05).</p><h3>Conclusions</h3><p>Chronic exposure to NP at environmental concentration could cause immune dysfunction, resulting in immunotoxicity and inflammatory effects, and lead to changes in the activity of transcription factors and differential immune inflammatory factors in rats.</p><h3>Graphical Abstract</h3>\n <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\n </div>","PeriodicalId":54293,"journal":{"name":"Environmental Sciences Europe","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://enveurope.springeropen.com/counter/pdf/10.1186/s12302-022-00610-6","citationCount":"2","resultStr":"{\"title\":\"Effects of subchronic exposure of nonylphenol on the expression of immune-related factors and estrogen receptors in the spleen of rats\",\"authors\":\"Xiangjun Fu, Jie Xu, Chengyu Ni, Degang Yu, Haibo Wang, Pan Wang, Man Luo, Jie Yu\",\"doi\":\"10.1186/s12302-022-00610-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Previous studies have shown that EDCs may activate nuclear transcription factor, such as activator protein-1 (AP-1), nuclear factor of activated Tcells (NF-AT) and nuclear factor kappa B (NF-κB) in the process of immune damage. At the same time, some experts believed that estrogen may play an important role in this process. As a typical representative of EDCs, nonylphenol (NP) has not been reported. The aim of this work was to explore the relationship between the immune inflammatory damage and the changes in estrogen expression in male rats during the chronic exposure to NP at environmental concentrations. Sixty SPF Sprague–Dawley rats were divided into five groups (<i>n</i> = 12 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E<sub>2</sub>: 30 μg/kg/d).</p><h3>Results</h3><p>Compared with the control group, rat spleen organ coefficient, number of spleen nodules, relative area of lymph nodes and white pulp were relatively reduced in the L (NP, 0.4 mg/kg) and H (NP, 40 mg/kg) exposure dose groups (<i>P</i> < 0.001). Lymphocytes were rich in cytoplasm, mitochondria were swollen, part of the cristae was reduced, and rough endoplasmic reticulum was expanded. The serum levels of IgG (<i>P</i> < 0.001) and IgM (<i>P</i> = 0.002) showed a downward trend. The percentage of Th cells (CD3<sup>+</sup>CD4<sup>+</sup>) was significantly decreased (<i>P</i> < 0.001), and the percentage of B lymphocytes shows an opposite trend (<i>P</i> < 0.001). Giemsa staining showed that the number of neutrophils (<i>P</i> < 0.001) was increased. The expressions of estrogen receptor ER-α and ER-β protein in the spleen increased significantly (<i>P</i> < 0.001). The expressions of AP-1 protein and NF-AT protein in the spleen were increased, and the expression of NF-KB protein was decreased (<i>P</i> < 0.001). The expressions of IL-4, ER-α and ER-β (<i>P</i> < 0.001) levels in serum increased. The mRNA-seq bioinformatics detection showed the final differentially expressed immune-inflammatory-related genes between the control and H-NP groups as follow: down-regulated: TLR4, Gata3, IL12, up-regulated: TNF-a, IL10, INOS. The mRNA expressions of ER-α, ER-β, NF-KB, IL4, AP-1, TLR4, Gata3, and NF-AT were consistent with the results of mRNA-seq analysis. NP content was correlated with the expressions of ER-α, ER-β, IL4, AP-1, NF-AT, TLR4, NF-KB, as well as IL-12 proteins in the spleen tissue ([<i>r</i>] < 1, <i>P</i> < 0.05).</p><h3>Conclusions</h3><p>Chronic exposure to NP at environmental concentration could cause immune dysfunction, resulting in immunotoxicity and inflammatory effects, and lead to changes in the activity of transcription factors and differential immune inflammatory factors in rats.</p><h3>Graphical Abstract</h3>\\n <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\\n </div>\",\"PeriodicalId\":54293,\"journal\":{\"name\":\"Environmental Sciences Europe\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2022-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://enveurope.springeropen.com/counter/pdf/10.1186/s12302-022-00610-6\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environmental Sciences Europe\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s12302-022-00610-6\",\"RegionNum\":3,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Environmental Science\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Sciences Europe","FirstCategoryId":"93","ListUrlMain":"https://link.springer.com/article/10.1186/s12302-022-00610-6","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Environmental Science","Score":null,"Total":0}
Effects of subchronic exposure of nonylphenol on the expression of immune-related factors and estrogen receptors in the spleen of rats
Background
Previous studies have shown that EDCs may activate nuclear transcription factor, such as activator protein-1 (AP-1), nuclear factor of activated Tcells (NF-AT) and nuclear factor kappa B (NF-κB) in the process of immune damage. At the same time, some experts believed that estrogen may play an important role in this process. As a typical representative of EDCs, nonylphenol (NP) has not been reported. The aim of this work was to explore the relationship between the immune inflammatory damage and the changes in estrogen expression in male rats during the chronic exposure to NP at environmental concentrations. Sixty SPF Sprague–Dawley rats were divided into five groups (n = 12 per group): blank control group (corn oil), low-dose NP exposure group (0.4 mg/kg/d), medium-dose NP exposure group (4 mg/kg/d), high-dose NP exposure group (40 mg/kg/d), and estradiol control group (E2: 30 μg/kg/d).
Results
Compared with the control group, rat spleen organ coefficient, number of spleen nodules, relative area of lymph nodes and white pulp were relatively reduced in the L (NP, 0.4 mg/kg) and H (NP, 40 mg/kg) exposure dose groups (P < 0.001). Lymphocytes were rich in cytoplasm, mitochondria were swollen, part of the cristae was reduced, and rough endoplasmic reticulum was expanded. The serum levels of IgG (P < 0.001) and IgM (P = 0.002) showed a downward trend. The percentage of Th cells (CD3+CD4+) was significantly decreased (P < 0.001), and the percentage of B lymphocytes shows an opposite trend (P < 0.001). Giemsa staining showed that the number of neutrophils (P < 0.001) was increased. The expressions of estrogen receptor ER-α and ER-β protein in the spleen increased significantly (P < 0.001). The expressions of AP-1 protein and NF-AT protein in the spleen were increased, and the expression of NF-KB protein was decreased (P < 0.001). The expressions of IL-4, ER-α and ER-β (P < 0.001) levels in serum increased. The mRNA-seq bioinformatics detection showed the final differentially expressed immune-inflammatory-related genes between the control and H-NP groups as follow: down-regulated: TLR4, Gata3, IL12, up-regulated: TNF-a, IL10, INOS. The mRNA expressions of ER-α, ER-β, NF-KB, IL4, AP-1, TLR4, Gata3, and NF-AT were consistent with the results of mRNA-seq analysis. NP content was correlated with the expressions of ER-α, ER-β, IL4, AP-1, NF-AT, TLR4, NF-KB, as well as IL-12 proteins in the spleen tissue ([r] < 1, P < 0.05).
Conclusions
Chronic exposure to NP at environmental concentration could cause immune dysfunction, resulting in immunotoxicity and inflammatory effects, and lead to changes in the activity of transcription factors and differential immune inflammatory factors in rats.
期刊介绍:
ESEU is an international journal, focusing primarily on Europe, with a broad scope covering all aspects of environmental sciences, including the main topic regulation.
ESEU will discuss the entanglement between environmental sciences and regulation because, in recent years, there have been misunderstandings and even disagreement between stakeholders in these two areas. ESEU will help to improve the comprehension of issues between environmental sciences and regulation.
ESEU will be an outlet from the German-speaking (DACH) countries to Europe and an inlet from Europe to the DACH countries regarding environmental sciences and regulation.
Moreover, ESEU will facilitate the exchange of ideas and interaction between Europe and the DACH countries regarding environmental regulatory issues.
Although Europe is at the center of ESEU, the journal will not exclude the rest of the world, because regulatory issues pertaining to environmental sciences can be fully seen only from a global perspective.