博碩士論文 110821015 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:110 、訪客IP:18.217.10.200
姓名 林晏如(Yen-Ju Lin)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 PM2.5 暴露對人類結腸腺癌 Caco-2 細胞的不良影響 -氧化壓力、發炎、細胞增殖及自噬損傷
(Adverse effects of PM2.5 exposure in human colonic adenocarcinoma Caco-2 cells-oxidative stress, inflammation, cell proliferation, and autophagy flux impairment)
相關論文
★ 雙酚混合物對斑馬魚胚胎心跳減緩的影響:鈣離子幫浦與鈣離子通道的參與★ 自然殺手細胞過繼免疫療法延長低度遠端轉移乳癌小鼠的生存期及增強肺部樹突狀細胞和 T 細胞的活化
★ 研究PM2.5引起腸道細胞不良反應的相關機制:氧化壓力調控引起發炎反應、細胞增生以及細胞自噬的產生★ 環狀BMP-2肽對肌原細胞中BMP-2蛋白信號的上調
★ 左旋硒代胱胺酸抑制Nrf2與細胞自噬訊息途徑導致Nrf2成癮的結直腸癌細胞死亡★ 內質網靶向藥物L-硒胱胺酸破壞蛋白質平衡並誘導大腸直腸癌細胞發生免疫原性細胞死亡
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2028-7-19以後開放)
摘要(中) Particulate matter (PM) 2.5是一種直徑小於或等於2.5直徑的懸浮微粒。大部分來源來自人為排放,其中包括工業燃燒和汽機車排放的廢氣。目前,PM 2.5已被國際癌症研究機構(International Agency for Research on Cancer, IARC)認定為一級致癌物,可通過呼吸系統進入人體,造成肺部損害,引發呼吸系統疾病,甚至進一步引發心血管疾病。此外,長期接觸 PM 2.5與結直腸癌(colorectal cancer, CRC)的癌症進展和死亡率相關。多項研究報告稱,PM 2.5改變了腸道微生物菌群並使其失衡,可能進一步導致代謝疾病和炎症,然而,分子信號傳導機制仍不清楚。本研究中,使用購自美國的標準品SRM (standard reference material of fine particulate matter) 2786在不同的暴露濃度與時間下,探討SRM 2786對Caco-2結腸腺癌的不良反應。我們發現在SRM 2786 處理的Caco-2中,能引起細胞增殖、活性氧(Reactive oxygen species, ROS)產生、環氧合酶 (Cyclooxygenase-2, COX-2)、粘著斑激酶 (Focal adhesion kinase, FAK)磷酸化、NF-kB (Nuclear Factor kappa-light-chain-enhancer of activated B cells)途徑中p65磷酸化及IL-1 beta (Interlukin-1 beta)表現量顯著增加。而抗氧化劑 (Glutathione, GSH)可顯著降低暴露於 SRM 2786的Caco-2細胞中ROS的產生和細胞增殖, NADPH oxidase 1 (NOX-1)及NADPH oxidase 4 (NOX-4)抑制劑也可顯著減少ROS的產生,SRM 2786還會增加了血紅素加氧酶 1 (Heme oxygenase-1, HO-1)和NAD(P)H-醌氧化還原酶 1 (NQO1)抗氧化酶的表現量,另外,以COX-2及FAK的抑制劑可顯著降低細胞增殖。同時,SRM 2786增加了LC3II和p62的表現量並引發溶酶體膜完整性的喪失,這些結果顯示 SRM 2786損害了自噬活化和溶酶體功能,損害細胞自噬流(autophagic flux)。暴露SRM 2786亦會導致Occludin及TJP2 (Tight junction protein 2)增加而ZO-1 (zonula occludens-1)則是減少,代表有可能損傷腸道基本屏障的功能,因此,SRM 2786對大腸癌細胞造成氧化壓力、發炎反應、細胞增殖和自噬損傷等不良反應,有可能會增加大腸癌的風險。
摘要(英) Particulate matter (PM) 2.5 is a fine particulate matter with a diameter less than or equal to 2.5 μm. Common sources come from anthropogenic emissions, which include industrial combustion and emissions from automobiles and locomotives. At present, PM2.5 has been identified as a primary carcinogen by the International Agency for Research on Cancer (IARC), which can enter the human body through the respiratory system, causing lung damage, respiratory diseases, and even further cardiovascular diseases. Furthermore, long-term exposure to PM2.5 is associated with cancer progression and mortality in colorectal cancer (CRC). Several studies have reported that PM alters and unbalances the gut microbiota, which may further contribute to metabolic disease and inflammation. However, the molecular signaling mechanism remains unclear. In this study, the standard reference material of fine particulate matter (SRM) 2786 purchased from the United States was used to investigate the adverse effects of SRM 2786 on Caco-2 colon adenocarcinoma under different exposure concentrations and time. We found that in SRM 2786-treated Caco-2, cell proliferation, Reactive oxygen species (ROS) production, cyclooxygenase (COX-2), Focal adhesion kinase (FAK) phosphorylation, p65 phosphorylation in NF-kB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) pathway, and IL-1 beta (Interlukin-1 beta) levels increased significantly. Antioxidant GSH (Glutathione) can significantly reduce ROS production and cell proliferation in Caco-2 cells exposed to SRM 2786. NADPH oxidase 1 (NOX-1) and NADPH oxidase 4 (NOX-4) inhibitors can also significantly reduce ROS levels in Caco-2 cells after SRM 2786 exposures. PM also increased the levels of Heme oxygenase 1 (HO-1) and NAD(P)H-quinone oxidoreductase 1 (NQO1) antioxidant enzymes. In addition, inhibitors of COX-2 and FAK can significantly reduce cell proliferation. Meanwhile, SRM 2786 increased the levels of LC3II and p62 and triggered the loss of lysosomal membrane integrity, suggesting that SRM 2786 impaired autophagic flux and lysosomal function. Exposure to SRM 2786 also resulted in an increase in Occludin and TJP2 (Tight junction protein 2) and a decrease in ZO-1 (zonula occludens-1), which may impair the function of the basic intestinal barrier Our results suggest that adverse effects of SRM 2786 exposure on CRC cells include oxidative stress, inflammation, cell proliferation, and autophagy impairment, which may increase the risk of CRC.
關鍵字(中) ★ 細胞自噬
★ 大腸癌
★ 氧化壓力
關鍵字(英) ★ PM2.5
論文目次 中文摘要 I
Abstract II
致謝 III
目錄 IV
圖目錄 VI
縮寫檢索表 VII
第一章 緒論 1
1.1懸浮微粒 (Particulate Matter) 1
1.2 SRM 2786 (Standard reference material of fine particulate matter 2786) 2
1.3活性氧與抗氧化路徑ROS (Reactive oxygen species) and Nrf2(Nuclear factor erythroid 2-related factor 2) pathway 3
1.4細胞自噬 (Autophagy) 4
1.5緊密連接 (Tight junction) 5
1.6 NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) 6
第二章 研究動機 8
第三章 實驗材料與方法 8
3.1實驗材料 9
3.1.1實驗細胞株 9
3.1.2實驗材料 9
3.1.3 試劑 9
3.1.4 耗材 10
3.1.5 儀器 11
3.2實驗方法 11
3.2.1 Caco-2培養方式 11
3.2.2 SRM 2786製備方式 12
3.2.3 BCA蛋白質濃度測定 ( Pierce™ BCA Protein Assay ) 12
3.2.4西方墨點法 ( Western Blot ) 13
3.2.5細胞增殖檢測 (Cell Counting Kit-8, CCK-8 assay) 14
3.2.6活性氧檢測 (2′,7′-Dichlorodihydrofluorescein diacetate, DCF-DA assay) 15
2.2.7免疫螢光染色及共同免疫螢光染色 (Immunofluorescence Staining and Co-immunofluorescent staining) 15
3.2.8活染溶酶體 (BioTracker 560 Orange Lysosome Dye) 16
3.2.9 細胞存活率試驗(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT Assay) 16
第四章 結果 17
4.1 Caco-2細胞在SRM 2786的暴露下引起細胞增生 17
4.2 Caco-2細胞在SRM 2786的暴露下引發氧化壓力和抗氧化機制 17
4.3 Caco-2在SRM 2786暴露下引發COX-2訊號活化 18
4.4 Caco-2細胞在SRM 2786的暴露下引起NF-κB活化 18
4.5 Caco-2在SRM 2786暴露下引發IL-1 Beta表現增加 19
4.6 Caco-2細胞在SRM 2786的暴露下引發細胞自噬反應失調 19
4.8 Caco-2細胞在SRM 2786的暴露下引起 FAK (Focal Adhesion Kinase)異常表現 21
4.9 Caco-2細胞在SRM 2786的暴露下引起 tight junction異常表現 22
第五章 討論 23
第六章 參考文獻 28
圖 37
附錄一 55
參考文獻 1. Lehtipalo, K., et al., Multicomponent new particle formation from sulfuric acid, ammonia, and biogenic vapors. Sci Adv, 2018. 4(12): p. eaau5363.
2. Verma, V., et al., Organic aerosols associated with the generation of reactive oxygen species (ROS) by water-soluble PM2.5. Environ Sci Technol, 2015. 49(7): p. 4646-56.
3. Chan, A.W.H., et al., Detailed chemical characterization of unresolved complex mixtures in atmospheric organics: Insights into emission sources, atmospheric processing, and secondary organic aerosol formation. Journal of Geophysical Research: Atmospheres, 2013. 118(12): p. 6783-6796.
4. Schlesinger, R.B., The health impact of common inorganic components of fine particulate matter (PM2.5) in ambient air: a critical review. Inhal Toxicol, 2007. 19(10): p. 811-32.
5. Kleeman, M.J. and G.R. Cass, Source contributions to the size and composition distribution of urban particulate air pollution. Atmospheric Environment, 1998. 32(16): p. 2803-2816.
6. Burkholder, J.B., et al., The Essential Role for Laboratory Studies in Atmospheric Chemistry. Environ Sci Technol, 2017. 51(5): p. 2519-2528.
7. Shiraiwa, M., et al., Aerosol Health Effects from Molecular to Global Scales. Environ Sci Technol, 2017. 51(23): p. 13545-13567.
8. Jimenez, J.L., et al., Evolution of organic aerosols in the atmosphere. Science, 2009. 326(5959): p. 1525-9.
9. Mentel, T.F., et al., Secondary aerosol formation from stress-induced biogenic emissions and possible climate feedbacks. Atmos. Chem. Phys., 2013. 13(17): p. 8755-8770.
10. Shakya, K.M. and R.J. Griffin, Secondary organic aerosol from photooxidation of polycyclic aromatic hydrocarbons. Environ Sci Technol, 2010. 44(21): p. 8134-9.
11. Lin, Y., et al., A Review of Recent Advances in Research on PM(2.5) in China. Int J Environ Res Public Health, 2018. 15(3).
12. Philip, S., et al., Anthropogenic fugitive, combustion and industrial dust is a significant, underrepresented fine particulate matter source in global atmospheric models. Environmental Research Letters, 2017. 12(4): p. 044018.
13. Al-Kindi, S.G., et al., Environmental determinants of cardiovascular disease: lessons learned from air pollution. Nat Rev Cardiol, 2020. 17(10): p. 656-672.
14. Shou, Y., et al., A review of the possible associations between ambient PM2.5 exposures and the development of Alzheimer′s disease. Ecotoxicol Environ Saf, 2019. 174: p. 344-352.
15. Hayes, R.B., et al., PM2.5 air pollution and cause-specific cardiovascular disease mortality. Int J Epidemiol, 2020. 49(1): p. 25-35.
16. Air pollution and cancer.
17. Wong, C.M., et al., Cancer Mortality Risks from Long-term Exposure to Ambient Fine Particle. Cancer Epidemiol Biomarkers Prev, 2016. 25(5): p. 839-45.
18. Guo, C., et al., Long-term exposure to ambient fine particles and gastrointestinal cancer mortality in Taiwan: A cohort study. Environ Int, 2020. 138: p. 105640.
19. Ethan, C.J., et al., Association between PM2.5 and mortality of stomach and colorectal cancer in Xi’an: a time-series study. Environmental Science and Pollution Research, 2020. 27(18): p. 22353-22363.
20. Beamish, L.A., A.R. Osornio-Vargas, and E. Wine, Air pollution: An environmental factor contributing to intestinal disease. J Crohns Colitis, 2011. 5(4): p. 279-86.
21. Feng, J., et al., Impact of air pollution on intestinal redox lipidome and microbiome. Free Radic Biol Med, 2020. 151: p. 99-110.
22. Salim, S.Y., G.G. Kaplan, and K.L. Madsen, Air pollution effects on the gut microbiota: a link between exposure and inflammatory disease. Gut Microbes, 2014. 5(2): p. 215-9.
23. Zhao, J., et al., Role of PM(2.5) in the development and progression of COPD and its mechanisms. Respir Res, 2019. 20(1): p. 120.
24. Thangavel, P., D. Park, and Y.C. Lee, Recent Insights into Particulate Matter (PM(2.5))-Mediated Toxicity in Humans: An Overview. Int J Environ Res Public Health, 2022. 19(12).
25. Brito, J., et al., Physical–chemical characterisation of the particulate matter inside two road tunnels in the São Paulo Metropolitan Area. Atmos. Chem. Phys., 2013. 13(24): p. 12199-12213.
26. Park, J., et al., Reactive oxygen species (ROS) activity of ambient fine particles (PM(2.5)) measured in Seoul, Korea. Environ Int, 2018. 117: p. 276-283.
27. Viehmann, A., et al., Long-term residential exposure to urban air pollution, and repeated measures of systemic blood markers of inflammation and coagulation. Occup Environ Med, 2015. 72(9): p. 656-63.
28. Tripathy, S., et al., Long-Term Ambient Air Pollution Exposures and Circulating and Stimulated Inflammatory Mediators in a Cohort of Midlife Adults. Environ Health Perspect, 2021. 129(5): p. 57007.
29. Mutlu, E.A., et al., Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice. Part Fibre Toxicol, 2011. 8: p. 19.
30. Kim, K.H., E. Kabir, and S. Kabir, A review on the human health impact of airborne particulate matter. Environ Int, 2015. 74: p. 136-43.
31. Karottki, D.G., et al., Cardiovascular and lung function in relation to outdoor and indoor exposure to fine and ultrafine particulate matter in middle-aged subjects. Environ Int, 2014. 73: p. 372-81.
32. Wise, S.A., et al., Standard reference materials (SRMs) for determination of organic contaminants in environmental samples. Analytical and Bioanalytical Chemistry, 2006. 386(4): p. 1153-1190.
33. Schantz, M.M., et al., Development of two fine particulate matter standard reference materials (<4 μm and <10 μm) for the determination of organic and inorganic constituents. Anal Bioanal Chem, 2016. 408(16): p. 4257-66.
34. Tait, S.W. and D.R. Green, Mitochondria and cell signalling. J Cell Sci, 2012. 125(Pt 4): p. 807-15.
35. Ward, J.P.T., From Physiological Redox Signalling to Oxidant Stress. Adv Exp Med Biol, 2017. 967: p. 335-342.
36. Son, B., et al., CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms. Am J Physiol Lung Cell Mol Physiol, 2017. 313(5): p. L916-L929.
37. Garçon, G., et al., Effect of Fe(2)O(3) on the capacity of benzo(a)pyrene to induce polycyclic aromatic hydrocarbon-metabolizing enzymes in the respiratory tract of Sprague-Dawley rats. Toxicol Lett, 2004. 150(2): p. 179-89.
38. Vakharia, D.D., et al., Effect of metals on polycyclic aromatic hydrocarbon induction of CYP1A1 and CYP1A2 in human hepatocyte cultures. Toxicol Appl Pharmacol, 2001. 170(2): p. 93-103.
39. Fetterman, J.L., M.J. Sammy, and S.W. Ballinger, Mitochondrial toxicity of tobacco smoke and air pollution. Toxicology, 2017. 391: p. 18-33.
40. Jin, X., et al., Mitochondrial damage mediated by ROS incurs bronchial epithelial cell apoptosis upon ambient PM(2.5) exposure. J Toxicol Sci, 2018. 43(2): p. 101-111.
41. Xia, T., M. Kovochich, and A.E. Nel, Impairment of mitochondrial function by particulate matter (PM) and their toxic components: implications for PM-induced cardiovascular and lung disease. Front Biosci, 2007. 12: p. 1238-46.
42. Pardo, M., et al., Nrf2 protects against diverse PM(2.5) components-induced mitochondrial oxidative damage in lung cells. Sci Total Environ, 2019. 669: p. 303-313.
43. Li, N., et al., Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect, 2003. 111(4): p. 455-60.
44. Gualtieri, M., et al., Winter fine particulate matter from Milan induces morphological and functional alterations in human pulmonary epithelial cells (A549). Toxicol Lett, 2009. 188(1): p. 52-62.
45. Hu, L., X. Yao, and Y. Shen, Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis. Sci Rep, 2016. 6: p. 35859.
46. Zheng, L., et al., Signal Transductions of BEAS-2B Cells in Response to Carcinogenic PM(2.5) Exposure Based on a Microfluidic System. Anal Chem, 2017. 89(10): p. 5413-5421.
47. Pardo, M., et al., Particulate Matter Toxicity Is Nrf2 and Mitochondria Dependent: The Roles of Metals and Polycyclic Aromatic Hydrocarbons. Chemical Research in Toxicology, 2020. 33(5): p. 1110-1120.
48. Dietrich, C., Antioxidant Functions of the Aryl Hydrocarbon Receptor. Stem Cells Int, 2016. 2016: p. 7943495.
49. Jaiswal, A.K., Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med, 2004. 36(10): p. 1199-207.
50. Kaspar, J.W., S.K. Niture, and A.K. Jaiswal, Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med, 2009. 47(9): p. 1304-9.
51. Keep, R.F., Y. Hua, and G. Xi, Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol, 2012. 11(8): p. 720-31.
52. Ahmed, S.M., et al., Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis, 2017. 1863(2): p. 585-597.
53. Cattani-Cavalieri, I., et al., Acute Exposure to Diesel-Biodiesel Particulate Matter Promotes Murine Lung Oxidative Stress by Nrf2/HO-1 and Inflammation Through the NF-kB/TNF-α Pathways. Inflammation, 2019. 42(2): p. 526-537.
54. Chan, J.K., et al., Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs. Part Fibre Toxicol, 2013. 10: p. 34.
55. Cho, H.Y. and S.R. Kleeberger, Noblesse oblige: NRF2 functions in the airways. Am J Respir Cell Mol Biol, 2014. 50(5): p. 844-7.
56. Liu, Q., Y. Gao, and X. Ci, Role of Nrf2 and Its Activators in Respiratory Diseases. Oxid Med Cell Longev, 2019. 2019: p. 7090534.
57. Orona, N.S., et al., Direct and Indirect Effect of Air Particles Exposure Induce Nrf2-Dependent Cardiomyocyte Cellular Response In Vitro. Cardiovasc Toxicol, 2019. 19(6): p. 575-587.
58. Wittkopp, S., et al., Nrf2-related gene expression and exposure to traffic-related air pollution in elderly subjects with cardiovascular disease: An exploratory panel study. J Expo Sci Environ Epidemiol, 2016. 26(2): p. 141-9.
59. Rubio, V., M. Valverde, and E. Rojas, Effects of atmospheric pollutants on the Nrf2 survival pathway. Environ Sci Pollut Res Int, 2010. 17(2): p. 369-82.
60. Okubo, T., M. Hosaka, and D. Nakae, In vitro effects induced by diesel exhaust at an air-liquid interface in a human lung alveolar carcinoma cell line A549. Exp Toxicol Pathol, 2015. 67(7-8): p. 383-8.
61. Klein, S.G., et al., Endothelial responses of the alveolar barrier in vitro in a dose-controlled exposure to diesel exhaust particulate matter. Part Fibre Toxicol, 2017. 14(1): p. 7.
62. Eskelinen, E.L., Autophagy: Supporting cellular and organismal homeostasis by self-eating. Int J Biochem Cell Biol, 2019. 111: p. 1-10.
63. Roscioli, E., et al., Airway epithelial cells exposed to wildfire smoke extract exhibit dysregulated autophagy and barrier dysfunction consistent with COPD. Respir Res, 2018. 19(1): p. 234.
64. Tan, W.S.D., et al., Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells. Toxicol Appl Pharmacol, 2018. 360: p. 120-130.
65. Yoshii, S.R. and N. Mizushima, Monitoring and Measuring Autophagy. Int J Mol Sci, 2017. 18(9).
66. Katsuragi, Y., Y. Ichimura, and M. Komatsu, p62/SQSTM1 functions as a signaling hub and an autophagy adaptor. Febs j, 2015. 282(24): p. 4672-8.
67. Zhao, X., et al., Autophagic flux blockage in alveolar epithelial cells is essential in silica nanoparticle-induced pulmonary fibrosis. Cell Death & Disease, 2019. 10(2): p. 127.
68. Ma, X., et al., Gold Nanoparticles Induce Autophagosome Accumulation through Size-Dependent Nanoparticle Uptake and Lysosome Impairment. ACS Nano, 2011. 5(11): p. 8629-8639.
69. Dikic, I. and Z. Elazar, Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol, 2018. 19(6): p. 349-364.
70. Bialik, S., S.K. Dasari, and A. Kimchi, Autophagy-dependent cell death - where, how and why a cell eats itself to death. J Cell Sci, 2018. 131(18).
71. Xiao, M., et al., Role of autophagy and apoptosis in wound tissue of deep second-degree burn in rats. Acad Emerg Med, 2014. 21(4): p. 383-91.
72. Eisenberg-Lerner, A., et al., Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death & Differentiation, 2009. 16(7): p. 966-975.
73. Foerster, E.G., et al., How autophagy controls the intestinal epithelial barrier. Autophagy, 2022. 18(1): p. 86-103.
74. Asano, J., et al., Intrinsic Autophagy Is Required for the Maintenance of Intestinal Stem Cells and for Irradiation-Induced Intestinal Regeneration. Cell Rep, 2017. 20(5): p. 1050-1060.
75. Matsuzawa-Ishimoto, Y., et al., Autophagy protein ATG16L1 prevents necroptosis in the intestinal epithelium. J Exp Med, 2017. 214(12): p. 3687-3705.
76. Burger, E., et al., Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation. Cell Host Microbe, 2018. 23(2): p. 177-190 e4.
77. Pott, J., A.M. Kabat, and K.J. Maloy, Intestinal Epithelial Cell Autophagy Is Required to Protect against TNF-Induced Apoptosis during Chronic Colitis in Mice. Cell Host Microbe, 2018. 23(2): p. 191-202.e4.
78. Balda, M.S. and K. Matter, Tight junctions and the regulation of gene expression. Biochim Biophys Acta, 2009. 1788(4): p. 761-7.
79. Martin, T.A. and W.G. Jiang, Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta, 2009. 1788(4): p. 872-91.
80. Brennan, K., et al., Tight junctions: a barrier to the initiation and progression of breast cancer? J Biomed Biotechnol, 2010. 2010: p. 460607.
81. Harhaj, N.S. and D.A. Antonetti, Regulation of tight junctions and loss of barrier function in pathophysiology. Int J Biochem Cell Biol, 2004. 36(7): p. 1206-37.
82. Turner, J.R., Molecular basis of epithelial barrier regulation: from basic mechanisms to clinical application. Am J Pathol, 2006. 169(6): p. 1901-9.
83. Cereijido, M., et al., New diseases derived or associated with the tight junction. Arch Med Res, 2007. 38(5): p. 465-78.
84. Dhawan, P., et al., Claudin-2 expression increases tumorigenicity of colon cancer cells: role of epidermal growth factor receptor activation. Oncogene, 2011. 30(29): p. 3234-47.
85. Suren, D., et al., Loss of tight junction proteins (Claudin 1, 4, and 7) correlates with aggressive behavior in colorectal carcinoma. Med Sci Monit, 2014. 20: p. 1255-62.
86. Johnson, A.H., et al., Expression of tight-junction protein claudin-7 is an early event in gastric tumorigenesis. Am J Pathol, 2005. 167(2): p. 577-84.
87. Dahiya, N., et al., Claudin-7 is frequently overexpressed in ovarian cancer and promotes invasion. PLoS One, 2011. 6(7): p. e22119.
88. Kortekaas Krohn, I., et al., Nasal epithelial barrier dysfunction increases sensitization and mast cell degranulation in the absence of allergic inflammation. Allergy, 2020. 75(5): p. 1155-1164.
89. Steelant, B., et al., Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol, 2016. 137(4): p. 1043-1053.e5.
90. Steelant, B., et al., Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis. J Allergy Clin Immunol, 2018. 141(3): p. 951-963 e8.
91. Tak, P.P. and G.S. Firestein, NF-kappaB: a key role in inflammatory diseases. J Clin Invest, 2001. 107(1): p. 7-11.
92. Shukla, A., et al., Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol, 2000. 23(2): p. 182-7.
93. Farooqi, Z.U., et al., Logical Analysis of Regulation of Interleukin-12 Expression Pathway Regulation During HCV Infection. Protein Pept Lett, 2016. 23(6): p. 581-9.
94. Oeckinghaus, A. and S. Ghosh, The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol, 2009. 1(4): p. a000034.
95. Westbrook, A.M., A. Szakmary, and R.H. Schiestl, Mechanisms of intestinal inflammation and development of associated cancers: lessons learned from mouse models. Mutat Res, 2010. 705(1): p. 40-59.
96. Tilstra, J.S., et al., NF-kappaB in Aging and Disease. Aging Dis, 2011. 2(6): p. 449-65.
97. Grivennikov, S.I., F.R. Greten, and M. Karin, Immunity, inflammation, and cancer. Cell, 2010. 140(6): p. 883-99.
98. Gambhir, S., et al., Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol, 2015. 21(11): p. 3174-83.
99. Lind, D.S., et al., Nuclear factor-kappa B is upregulated in colorectal cancer. Surgery, 2001. 130(2): p. 363-9.
100. Jimenez, L.A., et al., Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation. Toxicol Appl Pharmacol, 2000. 166(2): p. 101-10.
101. Nam, H.Y., et al., The role of nitric oxide in the particulate matter (PM2.5)-induced NFkappaB activation in lung epithelial cells. Toxicol Lett, 2004. 148(1-2): p. 95-102.
102. Rodriguez-Cotto, R.I., et al., African Dust Storms Reaching Puerto Rican Coast Stimulate the Secretion of IL-6 and IL-8 and Cause Cytotoxicity to Human Bronchial Epithelial Cells (BEAS-2B). Health (Irvine Calif), 2013. 5(10B): p. 14-28.
103. Wang, B., et al., Human bronchial epithelial cell injuries induced by fine particulate matter from sandstorm and non-sandstorm periods: Association with particle constituents. J Environ Sci (China), 2016. 47: p. 201-210.
104. Zhang, Z., et al., The effect of curcumin on human bronchial epithelial cells exposed to fine particulate matter: a predictive analysis. Molecules, 2012. 17(10): p. 12406-26.
105. Hashemi Goradel, N., et al., Cyclooxygenase-2 in cancer: A review. Journal of Cellular Physiology, 2019. 234(5): p. 5683-5699.
106. Milkovic, L., et al., Short Overview of ROS as Cell Function Regulators and Their Implications in Therapy Concepts. Cells, 2019. 8(8).
107. van der Post, S., G.M.H. Birchenough, and J.M. Held, NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation. Cell Rep, 2021. 35(1): p. 108949.
108. Yang, X., et al., NOX4 has the potential to be a biomarker associated with colon cancer ferroptosis and immune infiltration based on bioinformatics analysis. Front Oncol, 2022. 12: p. 968043.
109. Mohsin, N.u.A., et al., Cyclooxygenase-2 (COX-2) as a Target of Anticancer Agents: A Review of Novel Synthesized Scaffolds Having Anticancer and COX-2 Inhibitory Potentialities. Pharmaceuticals, 2022. 15(12): p. 1471.
110. Wang, Y., et al., Focal Adhesion Kinase Inhibitor Inhibits the Oxidative Damage Induced by Central Venous Catheter via Abolishing Focal Adhesion Kinase-Protein Kinase B Pathway Activation. Biomed Res Int, 2021. 2021: p. 6685493.
111. Ma, Y., et al., Focal adhesion kinase regulates intestinal epithelial barrier function via redistribution of tight junction. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2013. 1832(1): p. 151-159.
112. Zeisel, M.B., P. Dhawan, and T.F. Baumert, Tight junction proteins in gastrointestinal and liver disease. Gut, 2019. 68(3): p. 547-561.
113. Hoover, K.B., S.Y. Liao, and P.J. Bryant, Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity. Am J Pathol, 1998. 153(6): p. 1767-73.
114. Kaihara, T., et al., Dedifferentiation and decreased expression of adhesion molecules, E-cadherin and ZO-1, in colorectal cancer are closely related to liver metastasis. J Exp Clin Cancer Res, 2003. 22(1): p. 117-23.
115. Kimura, Y., et al., Expression of occludin, tight-junction-associated protein, in human digestive tract. Am J Pathol, 1997. 151(1): p. 45-54.
116. Resnick, M.B., et al., Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study. Mod Pathol, 2005. 18(4): p. 511-8.
117. Odenwald, M.A. and J.R. Turner, The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol, 2017. 14(1): p. 9-21.
118. Wang, M., et al., Downregulation of occludin affects the proliferation, apoptosis and metastatic properties of human lung carcinoma. Oncol Rep, 2018. 40(1): p. 454-462.
119. Betanzos, A., et al., The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription factors in epithelial cells. Exp Cell Res, 2004. 292(1): p. 51-66.
120. Aits, S., Methods to Detect Loss of Lysosomal Membrane Integrity. Methods Mol Biol, 2019. 1880: p. 315-329.
121. The Cell: A Molecular Approach. 2nd edition.
122. Wu, Y., et al., p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation. Journal of Nanobiotechnology, 2020. 18(1): p. 77.
123. Cliff, R., et al., Effect of diesel exhaust inhalation on blood markers of inflammation and neurotoxicity: a controlled, blinded crossover study. Inhal Toxicol, 2016. 28(3): p. 145-53.
124. Ligumsky, M., et al., Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease. Gut, 1990. 31(6): p. 686-9.
125. Isaacs, K.L., R.B. Sartor, and S. Haskill, Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology, 1992. 103(5): p. 1587-95.
126. Nemetz, A., et al., IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease. Immunogenetics, 1999. 49(6): p. 527-31.
127. Ma, T.Y., et al., TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol, 2004. 286(3): p. G367-76.
128. Stevens, C., et al., Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci, 1992. 37(6): p. 818-26.
129. Al-Sadi, R.M. and T.Y. Ma, IL-1beta causes an increase in intestinal epithelial tight junction permeability. J Immunol, 2007. 178(7): p. 4641-9.
指導教授 羅月霞(Yueh-Hsia Luo) 審核日期 2023-7-20
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明