雌激素受体作为壬基酚的主要作用靶点导致机体免疫毒性
|
摘要
雌激素作为一类重要的性腺类固醇化学信使,已经被证实能够直接调节机体免疫反应,因此,一些具有拟雌激素特性的环境内分泌干扰物(endocrine disruptors,EDs),会通过影响雌激素相关信号通路对免疫系统产生干扰作用。壬基酚(nonylphenol,NP)作为典型的环境内分泌干扰物,已有大量的文献报道其通过拟雌激素特性或干扰雌激素的合成、分泌、转运以及与靶点的结合,破坏机体生殖功能以及神经-免疫-内分泌系统,影响整体生理平衡与稳定。近年来,NP对免疫系统的干扰作用逐渐引起重视,研究发现,NP暴露会引起小鼠免疫器官及免疫细胞的发育异常,并且会导致新生小鼠肝毒性,肝脏细胞内炎性因子TNF-α、IL-1β分泌增加。除NP作为配体干扰雌激素信号通路外,尚未发现其他明确的分子机制解释NP造成的免疫毒性。本综述主要结合近年来相关的实验结果,总结了NP对免疫系统的潜在影响及其可能的分子机制。
Estrogen acts as a chemical messenger in target tissues regulating immune responses,and therefore estrogen-like endocrine disrupting chemical can act on estrogen-mediated signal transduction pathway and induce damage to immune system. Nonylphenol( NP),an endocrine disrupting chemical with estrogen-like effects,can interfere with the synthesis,secretion and transport of estrogen,and disrupt reproductive and neural-immunity-endocrine systems as well as physiological balance and stability in body. Previous studies revealed that NP exposure could cause the developmental disorders of immune organs and cells,which further could lead to hepatotoxicity that involved an increase in the secretion of TNF-α and IL-1β in mice. The mechanism is associated with the disruption of estrogen signaling pathway induced by NP. We summarize the key findings from the recent scientific literature,identify the potential effects of NP on immune system and its molecular mechanisms.
Estrogen acts as a chemical messenger in target tissues regulating immune responses,and therefore estrogen-like endocrine disrupting chemical can act on estrogen-mediated signal transduction pathway and induce damage to immune system. Nonylphenol( NP),an endocrine disrupting chemical with estrogen-like effects,can interfere with the synthesis,secretion and transport of estrogen,and disrupt reproductive and neural-immunity-endocrine systems as well as physiological balance and stability in body. Previous studies revealed that NP exposure could cause the developmental disorders of immune organs and cells,which further could lead to hepatotoxicity that involved an increase in the secretion of TNF-α and IL-1β in mice. The mechanism is associated with the disruption of estrogen signaling pathway induced by NP. We summarize the key findings from the recent scientific literature,identify the potential effects of NP on immune system and its molecular mechanisms.
引文
[1] Sun S S,Tan P C,Huang X H,et al. Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes[J].Journal of Biological Chemistry,2018,293:2383-2394
[2] Yu J,Luo Y,Yang X F,et al. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats[J]. Brazilian Journal of Medical and Biological Research,2016,49:e5647
[3] Khan D,Ahmed A S. The immune system is a natural target for estrogen action:Opposing effects of estrogen in two prototypical autoimmune diseases[J]. Frontiers in Immunology,2015,6:635
[4] Finlay G A,Malhowski A J,Liu Y,et al. Selective inhibition of growth of tuberous sclerosis complex 2 null cells by atorvastatin is associated with impaired Rheb and Rho GTPase function and reduced m TOR/S6 kinase activity[J].Cancer Research,2017,67(20):9878-9886
[5] Koh P O,Cho J H,Won C K,et al. Estradiol attenuates the focal cerebral ischemic injury through m TOR/p70S6 kinase signaling pathway[J]. Neuroscience Letters,2008,436:62-66
[6] Franco H L,Nagari A,Kraus W L. TNF alpha signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome[J]. Molecular Cell,2015,58:21-34
[7] Sun M,Gadad S S,Kim D S,et al. Discovery,annotation,and functional analysis of long noncoding RNAs controlling cell-cycle gene expression and proliferation in breast cancer cells[J]. Molecular Cell,2015,59:698-711
[8] Rubinow K B. An intracrine view of sex steroids,immunity,and metabolic regulation[J]. Molecular Metabolism,2018,15:92-103
[9] Gear R B,Belcher S M. Impacts of bisphenol A and ethinyl estradiol on male and female CD-1 mouse spleen[J]. Scientific Reports,2017,7:856
[10] Kim C,Cadet P. Environmental toxin 4-nonylphenol and autoimmune diseases:Using DNA microarray to examine genetic markers of cytokine expression[J]. Archives of Medical Science,2010,6:321-327
[11] Straub R H. The complex role of estrogens in inflammation[J]. Endocrine Reviews,2007,28:521-574
[12] Gibson B A,Zhang Y,Jiang H,et al. Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation[J]. Science,2016,353:45-50
[13] Kim J,Cha S,Lee M Y,et al. Chronic low-dose nonylphenol or di-(2-ethylhexyl)phthalate has a different estrogen-like response in mouse uterus[J]. Development&Reproduction,2018,22:379-391
[14] Hessel E V S,Ezendam J,van Broekhuizen F A,et al. Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI[J]. Reproductive Toxicology,2016,65:448-456
[15] Gabriel F L,Giger W,Guenther K,et al. Differential degradation of nonylphenol isomers by Sphingomonas xenophaga Bayram[J]. Applied and Environmental Microbiology,2005,71:1123-1129
[16] Casey S C,Vaccari M,Al-Mulla F,et al. The effect of environmental chemicals on the tumor microenvironment[J]. Carcinogenesis,2015,36(Suppl 1):S160-S183
[17] Robinson L,Miller R. The impact of bisphenol A and phthalates on allergy,asthma,and immune function:A review of latest findings[J]. Current Environmental Health Reports,2015,2:379-387
[18] Udoji F,Martin T,Etherton R,et al. Immunosuppressive effects of triclosan,nonylphenol,and DDT on human natural killer cells in vitro[J]. Journal of Immunotoxicology,2010,7:205-212
[19] Thompson P A,Khatami M B,Carolyn J S,et al. Environmental immune disruptors,inflammation and cancer risk[J]. Carcinogenesis,2015,36(Suppl 1):S232-S253
[20] Kravchenko J,Corsini E,Williams M A,et al. Chemical compounds from anthropogenic environment and immune evasion mechanisms:Potential interactions[J].Carcinogenesis,2015,36(Suppl 1):S111-S127
[21] Duarte J N,Cragnolini J J,Swee L K,et al. Generation of immunity against pathogens via single-domain antibody-antigen constructs[J]. Journal of Immunology,2016,197:4838-4847
[22] De Weert J,Vinas M,Grotenhuis T,et al. Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial cultures from sediments[J]. Applied Microbiology and Biotechnology,2010,86:761-771
[23] Yang O,Kim H L,Weon J I,et al. Endocrine-disrupting chemicals:Review of toxicological mechanisms using molecular pathway analysis[J]. Journal of Cancer Prevention,2015,20:12-24
[24] Yu J,Yang X S,Luo Y,et al. Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats[J]. PLoS ONE,2017,12:e0180218
[25] Sun H W,Hu H W,Wang L,et al. The bioconcentration and degradation of nonylphenol and nonylphenol polyethoxylates by Chlorella vulgaris[J]. International Journal of Molecular Sciences,2014,15:1255-1270
[26] Yu J,Yang X S,Luo Y,et al. Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats[J]. PLoS ONE,2017,12:e0180218
[27] Duarte J N,Cragnolini J J,Swee L K,et al. Generation of immunity against pathogens via single-domain antibody-antigen constructs[J]. Journal of Immunology,2016,197:4838-4847
[28] Magnifico M C,Xhani M,Popov M,et al. Nonylphenol and octylphenol differently affect cell redox balance by modulating the nitric oxide signaling[J]. Oxidative Medicine and Cellular Longevity,2018(3):1-13
[29] Yu C J,Du J C,Chiou H C,et al. Attention deficit/hyperactivity disorder and urinary nonylphenol levels:A case-control study in Taiwanese children[J]. PLoS ONE,2016,11:e0149558
[30] Mao Z,Zheng Y L,Zhang Y Q. Behavioral impairment and oxidative damage induced by chronic application of nonylphenol[J]. International Journal of Molecular Sciences,2010,12:114-127
[31] Yu J,Yang J,Luo Y,et al. The adverse effects of chronic low-dose exposure to nonylphenol on type 2 diabetes mellitus in high sucrose-high fat diet-treated rats[J].Islets,2018,10(13):e1404211
[32] Yang O,Kim H L,Weon J I,et al. Endocrine-disrupting chemicals:Review of toxicological mechanisms using molecular pathway analysis[J]. Journal of Cancer Prevention,2015,20:12-24
[33] De Weert J P,Vinas M,Grotenhuis T,et al. Degradation of 4-n-nonylphenol under nitrate reducing conditions[J]. Biodegradation,2011,22:175-187
[34] Arambourou H,Beisel J N,Branchu P,et al. Patterns of fluctuating asymmetry and shape variation in Chironomus riparius(Diptera,Chironomidae)exposed to nonylphenol or lead[J]. PLoS ONE,2012,7:e48844
[35] Min J,Han J,Kim K,et al. Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion[J].Medicine,2017,96:e7737
[36] Cheng G H,Sun M Y,Lu J R,et al. Role of biochar in biodegradation of nonylphenol in sediment:Increasing microbial activity versus decreasing bioavailability[J].Scientific Reports,2017,7:4726
[37] Calafat A M,Kuklenyik Z,Reidy J A,et al. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population[J]. Environmental Health Perspectives,2005,113:391-395
[38] Negishi T,Kawasaki K,Suzaki S,et al. Behavioral alterations in response to fear-provoking stimuli and tranylcypromine induced by perinatal exposure to bisphenol A and nonylphenol in male rats[J]. Environmental Health Perspectives,2004,112:1159-1164
[39] Lacorte S,Latorre A,Guillamon M,et al. Nonylphenol,octyphenol,and bisphenol A in groundwaters as a result of agronomic practices[J]. The Scientific World Journal,2002,2:1095-1100
[40]陆维晨．壬基酚对雄性SD大鼠生殖系统功能的影响[D]．苏州:苏州大学，2014:57-73
[41]周莉婷．壬基酚对SD大鼠胰腺功能的影响[D]．苏州:苏州大学，2016:41-47Zhou L T. Effects of nonylphenol on pancreatic function in SD rats[D]. Suzhou:Suzhou University,2016:41-47(in Chinese)
[42] Mota L C,Barfield C,Hernandez J P,et al. Nonylphenol-mediated CYP induction is PXR-dependent:The use of humanized mice and human hepatocytes suggests that h PXR is less sensitive than mouse PXR to nonylphenol treatment[J]. Toxicology and Applied Pharmacology,2011,252:259-267
[43] Breydo L,Morgan D,Uversky V N,et al. Pseudocatalytic antiaggregation activity of antibodies:Immunoglobulins can influenceα-synuclein aggregation at substoichiometric concentrations[J]. Molecular Neurobiology,2015,53(3):1949-1958
[44] Fan Y S,Li Q,Hamdan N,et al. Tetrahydroxystilbene glucoside regulates proliferation, differentiation, and OPG/RANKL/M-CSF expression in MC3T3-E1 cells via the PI3K/Akt pathway[J]. Molecules, 2018, 23:2306
[2] Yu J,Luo Y,Yang X F,et al. Effects of perinatal exposure to nonylphenol on delivery outcomes of pregnant rats and inflammatory hepatic injury in newborn rats[J]. Brazilian Journal of Medical and Biological Research,2016,49:e5647
[3] Khan D,Ahmed A S. The immune system is a natural target for estrogen action:Opposing effects of estrogen in two prototypical autoimmune diseases[J]. Frontiers in Immunology,2015,6:635
[4] Finlay G A,Malhowski A J,Liu Y,et al. Selective inhibition of growth of tuberous sclerosis complex 2 null cells by atorvastatin is associated with impaired Rheb and Rho GTPase function and reduced m TOR/S6 kinase activity[J].Cancer Research,2017,67(20):9878-9886
[5] Koh P O,Cho J H,Won C K,et al. Estradiol attenuates the focal cerebral ischemic injury through m TOR/p70S6 kinase signaling pathway[J]. Neuroscience Letters,2008,436:62-66
[6] Franco H L,Nagari A,Kraus W L. TNF alpha signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome[J]. Molecular Cell,2015,58:21-34
[7] Sun M,Gadad S S,Kim D S,et al. Discovery,annotation,and functional analysis of long noncoding RNAs controlling cell-cycle gene expression and proliferation in breast cancer cells[J]. Molecular Cell,2015,59:698-711
[8] Rubinow K B. An intracrine view of sex steroids,immunity,and metabolic regulation[J]. Molecular Metabolism,2018,15:92-103
[9] Gear R B,Belcher S M. Impacts of bisphenol A and ethinyl estradiol on male and female CD-1 mouse spleen[J]. Scientific Reports,2017,7:856
[10] Kim C,Cadet P. Environmental toxin 4-nonylphenol and autoimmune diseases:Using DNA microarray to examine genetic markers of cytokine expression[J]. Archives of Medical Science,2010,6:321-327
[11] Straub R H. The complex role of estrogens in inflammation[J]. Endocrine Reviews,2007,28:521-574
[12] Gibson B A,Zhang Y,Jiang H,et al. Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation[J]. Science,2016,353:45-50
[13] Kim J,Cha S,Lee M Y,et al. Chronic low-dose nonylphenol or di-(2-ethylhexyl)phthalate has a different estrogen-like response in mouse uterus[J]. Development&Reproduction,2018,22:379-391
[14] Hessel E V S,Ezendam J,van Broekhuizen F A,et al. Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI[J]. Reproductive Toxicology,2016,65:448-456
[15] Gabriel F L,Giger W,Guenther K,et al. Differential degradation of nonylphenol isomers by Sphingomonas xenophaga Bayram[J]. Applied and Environmental Microbiology,2005,71:1123-1129
[16] Casey S C,Vaccari M,Al-Mulla F,et al. The effect of environmental chemicals on the tumor microenvironment[J]. Carcinogenesis,2015,36(Suppl 1):S160-S183
[17] Robinson L,Miller R. The impact of bisphenol A and phthalates on allergy,asthma,and immune function:A review of latest findings[J]. Current Environmental Health Reports,2015,2:379-387
[18] Udoji F,Martin T,Etherton R,et al. Immunosuppressive effects of triclosan,nonylphenol,and DDT on human natural killer cells in vitro[J]. Journal of Immunotoxicology,2010,7:205-212
[19] Thompson P A,Khatami M B,Carolyn J S,et al. Environmental immune disruptors,inflammation and cancer risk[J]. Carcinogenesis,2015,36(Suppl 1):S232-S253
[20] Kravchenko J,Corsini E,Williams M A,et al. Chemical compounds from anthropogenic environment and immune evasion mechanisms:Potential interactions[J].Carcinogenesis,2015,36(Suppl 1):S111-S127
[21] Duarte J N,Cragnolini J J,Swee L K,et al. Generation of immunity against pathogens via single-domain antibody-antigen constructs[J]. Journal of Immunology,2016,197:4838-4847
[22] De Weert J,Vinas M,Grotenhuis T,et al. Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial cultures from sediments[J]. Applied Microbiology and Biotechnology,2010,86:761-771
[23] Yang O,Kim H L,Weon J I,et al. Endocrine-disrupting chemicals:Review of toxicological mechanisms using molecular pathway analysis[J]. Journal of Cancer Prevention,2015,20:12-24
[24] Yu J,Yang X S,Luo Y,et al. Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats[J]. PLoS ONE,2017,12:e0180218
[25] Sun H W,Hu H W,Wang L,et al. The bioconcentration and degradation of nonylphenol and nonylphenol polyethoxylates by Chlorella vulgaris[J]. International Journal of Molecular Sciences,2014,15:1255-1270
[26] Yu J,Yang X S,Luo Y,et al. Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats[J]. PLoS ONE,2017,12:e0180218
[27] Duarte J N,Cragnolini J J,Swee L K,et al. Generation of immunity against pathogens via single-domain antibody-antigen constructs[J]. Journal of Immunology,2016,197:4838-4847
[28] Magnifico M C,Xhani M,Popov M,et al. Nonylphenol and octylphenol differently affect cell redox balance by modulating the nitric oxide signaling[J]. Oxidative Medicine and Cellular Longevity,2018(3):1-13
[29] Yu C J,Du J C,Chiou H C,et al. Attention deficit/hyperactivity disorder and urinary nonylphenol levels:A case-control study in Taiwanese children[J]. PLoS ONE,2016,11:e0149558
[30] Mao Z,Zheng Y L,Zhang Y Q. Behavioral impairment and oxidative damage induced by chronic application of nonylphenol[J]. International Journal of Molecular Sciences,2010,12:114-127
[31] Yu J,Yang J,Luo Y,et al. The adverse effects of chronic low-dose exposure to nonylphenol on type 2 diabetes mellitus in high sucrose-high fat diet-treated rats[J].Islets,2018,10(13):e1404211
[32] Yang O,Kim H L,Weon J I,et al. Endocrine-disrupting chemicals:Review of toxicological mechanisms using molecular pathway analysis[J]. Journal of Cancer Prevention,2015,20:12-24
[33] De Weert J P,Vinas M,Grotenhuis T,et al. Degradation of 4-n-nonylphenol under nitrate reducing conditions[J]. Biodegradation,2011,22:175-187
[34] Arambourou H,Beisel J N,Branchu P,et al. Patterns of fluctuating asymmetry and shape variation in Chironomus riparius(Diptera,Chironomidae)exposed to nonylphenol or lead[J]. PLoS ONE,2012,7:e48844
[35] Min J,Han J,Kim K,et al. Human cholestatic hepatitis owing to polyoxyethylene nonylphenol ingestion[J].Medicine,2017,96:e7737
[36] Cheng G H,Sun M Y,Lu J R,et al. Role of biochar in biodegradation of nonylphenol in sediment:Increasing microbial activity versus decreasing bioavailability[J].Scientific Reports,2017,7:4726
[37] Calafat A M,Kuklenyik Z,Reidy J A,et al. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population[J]. Environmental Health Perspectives,2005,113:391-395
[38] Negishi T,Kawasaki K,Suzaki S,et al. Behavioral alterations in response to fear-provoking stimuli and tranylcypromine induced by perinatal exposure to bisphenol A and nonylphenol in male rats[J]. Environmental Health Perspectives,2004,112:1159-1164
[39] Lacorte S,Latorre A,Guillamon M,et al. Nonylphenol,octyphenol,and bisphenol A in groundwaters as a result of agronomic practices[J]. The Scientific World Journal,2002,2:1095-1100
[40]陆维晨．壬基酚对雄性SD大鼠生殖系统功能的影响[D]．苏州:苏州大学，2014:57-73
[41]周莉婷．壬基酚对SD大鼠胰腺功能的影响[D]．苏州:苏州大学，2016:41-47Zhou L T. Effects of nonylphenol on pancreatic function in SD rats[D]. Suzhou:Suzhou University,2016:41-47(in Chinese)
[42] Mota L C,Barfield C,Hernandez J P,et al. Nonylphenol-mediated CYP induction is PXR-dependent:The use of humanized mice and human hepatocytes suggests that h PXR is less sensitive than mouse PXR to nonylphenol treatment[J]. Toxicology and Applied Pharmacology,2011,252:259-267
[43] Breydo L,Morgan D,Uversky V N,et al. Pseudocatalytic antiaggregation activity of antibodies:Immunoglobulins can influenceα-synuclein aggregation at substoichiometric concentrations[J]. Molecular Neurobiology,2015,53(3):1949-1958
[44] Fan Y S,Li Q,Hamdan N,et al. Tetrahydroxystilbene glucoside regulates proliferation, differentiation, and OPG/RANKL/M-CSF expression in MC3T3-E1 cells via the PI3K/Akt pathway[J]. Molecules, 2018, 23:2306
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |