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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 康照洲 | |
| dc.contributor.author | Yi Lee | en |
| dc.contributor.author | 李儀 | zh_TW |
| dc.date.accessioned | 2021-06-17T03:12:42Z | - |
| dc.date.available | 2023-08-01 | |
| dc.date.copyright | 2018-08-01 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-07-13 | |
| dc.identifier.citation | Ajayi BO, Adedara IA, Farombi EO (2016) Benzo(a)pyrene induces oxidative stress, pro-inflammatory cytokines, expression of nuclear factor-kappa B and deregulation of wnt/beta-catenin signaling in colons of BALB/c mice. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 95:42-51 doi:10.1016/j.fct.2016.06.019
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69314 | - |
| dc.description.abstract | 近年來，許多研究發現PAHs可增加諸多眼部病變，流病資料統計亦發現抽菸與眼睛疾病發生有關。Benzo[a]pyrene (B[a]P)為多環芳香烴(Polycyclic Aromatic Hydrocarbons, PAHs)的其中之一員，由碳的不完全燃燒所產生，是一種廣泛存在環境的的致癌化學物質。B[a]P為Aryl Hydrocarbon Receptor (AhR) ligand，進入細胞後會和AhR蛋白結合進一步調控下游多項基因轉錄。過去研究顯示，B[a]P可能會透過AhR調控發炎反應，但具體機轉仍不清楚。Suppressor of cytokine signaling-3 (Socs3)作為一發炎調控因子，可藉由負回饋機轉抑制發炎反應，而發炎是導致視網膜病變的主要因素之一，因此本研究希望觀察眼部暴露B[a]P後之AhR路徑對Socs3的影響。我們利用ARPE-19人類視網膜色素上皮細胞株證實B[a]P暴露會透過活化AhR，近一步誘導Socs3表現；然而當AhR消失時，Socs3表現下降，但是隨B[a]P劑量暴露，依舊可以觀察到Socs3表現的誘導現象，伴隨Stat3的磷酸化增加。在炎症進展中，JAK / STAT途徑在信號轉導中起關鍵作用，後續實驗利用免疫熒光、免疫沈澱法以及Stat3磷酸化抑制劑證實在沒有AhR的情況下則會透過Stat3活化取代AhR增加Socs3表現。另外，過去文獻指出，B[a]P會導致發炎反應上升，然Socs3一般被認為扮演抑制發炎角色，所以接下來實驗想探討B[a]P對發炎的影響以及Socs3所扮演的角色。在以單一3µM B[a]P劑量24小時暴露後，測量發炎因子IL-6、TGF-beta1，並未發現以上發炎因子表現改變情況，相關B[a]P暴露對視網膜色素上皮細胞發炎的影響，仍待後續更全面劑量、暴露時間及不同cytokine的研究。 | zh_TW |
| dc.description.abstract | Recently, studies demonstrated that PAHs might increase a number of eye lesions. Statistics of epidemics suggested that smoking was a risk factor for oculardiseases. Benzo[a]pyrene (B[a]P), one of the polycyclic aromatic hydrocarbons (PAHs), a carcinogenic chemical substance that is widely present in the environment. It is produced by incomplete combustion of carbon. B[a]P is an aryl hydrocarbon receptor (AhR) ligand that binds to the AhR protein and further regulates downstream gene transcription. In addition, studies had also shown that B[a]P might affect the cellular inflammatory response through activation of the AhR pathway, but the relevant mechanisms remained unclear. Suppressor of cytokine signaling-3 (Socs3), an inflammatory regulator, act as an inhibitor of inflammation by negative feedback. Inflammation is one of the major causes of retinopathy. Therefore, this study aims to observe the effect of the AhR –regulated Socs3 pathway with B[a]P exposure. Here, we used ARPE-19 human retinal pigment epithelial cell line that B[a]P induced Socs3 expression through the activation of AhR. Knock out of AhR attenuated the B[a]P-dependent induction of Socs3 expression, accompanied with the increase of the phosphorylated Stat3. Subsequent experiments using immunofluorescence and Stat3 phosphorylation inhibitors demonstrated that in the absence of AhR, activation of Stat3 replaced AhR and increased the expression of Socs3. In addition, after exposure to 3 μM B[a]P for 24 hours, inflammatory cytokines IL-6 and TGF-beta1 were measured and no change in the protein expression was found. More studies should be done to further confirm the effect of B[a]P to ARPE-19 cells. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T03:12:42Z (GMT). No. of bitstreams: 1 ntu-107-R05447002-1.pdf: 4651014 bytes, checksum: a8a9c1d3ea6f6e564c8cdb8899b54a4f (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 中文摘要 1
英文摘要 2 第一章 緒論 3 1.1多環芳香烴 (Polycyclic aromatic hydrocarbons, PAHs) 與苯芘 (benzo[a]pyrene, B[a]P)毒理背景介紹 4 1.2 多環芳香烴受體 (Aryl hydrocarbon receptor, AhR) 6 1.3 多環芳香烴受體 (Aryl hydrocarbon receptor, AhR) 與發炎 7 1.4 細胞激素信號抑制3 (Suppressor of cytokine signaling 3, Socs3) 與免疫發炎 8 1.5 發炎反應對視網膜色素上皮細胞之影響 11 1.6研究動機 13 第二章 材料與方法 15 2.1 實驗材料 16 2.1.1 細胞株 (Cell lines) 16 2.1.2 藥品與試劑 (Chemicals and Reagents) 16 2.1.3 抗體 (Antibodies) 18 2.1.4 質體 (Plasmids) 18 2.2 實驗方法 18 2.2.1細胞培養 (Cell culture) 18 2.2.2 細胞總蛋白質液收集 (Cell lysate collection) 19 2.2.3 西方墨點法 (Western blot analysis) 20 2.2.4 免疫沉澱法 (Immunoprecipitation) 20 2.2.5質體萃取 (Plasmid DNA purification) 21 2.2.6質體轉染 (Plasmid transfection) 21 2.2.7 SIE冷光酵素分析法 (SIE luciferase assay) 22 2.2.8免疫螢光染色 (immunofluorescence staining) 22 2.2.9 反轉錄聚合酵素連鎖反應 (Reverse Transcription Polymerase Chain Reaction,RT-PCR) 23 2.2.10酵素連結免疫吸附法 (Enzyme-linked immunosorbent assay, ELISA) 24 2.2. 11統計分析 (Statistic analysis) 25 第三章 實驗結果 26 3.1 B[a]P會降低ARPE-19細胞中AhR蛋白表現 27 3.2 B[a]P會增加ARPE-19細胞中Socs3 mRNA以及蛋白表現 27 3.3 CH223191可以透過抑制AhR降低B[a]P所誘導的Socs3表現 28 3.4 B[a]P所誘導的Socs3表現在AhR-/- ARPE-19細胞株減弱，但仍存在 28 3.5 B[a]P暴露會活化AhR-/- ARPE-19的Stat3路徑 29 3.6 Nifuroxazide在AhR-/- ARPE-19細胞株可以透過抑制Stat3磷酸化降低B[a]P所誘導的Socs3表現 30 3.7 B[a]P在細胞缺乏AhR時會增加p-Stat3的入荷情況 31 3.8.B[a]P暴露上調AhR-/- ARPE-19細胞株SIE轉錄活性 31 3.9. AhR-/- ARPE-19細胞Socs3和Stat3交互作用相較AhR+/+細胞明顯增加 32 3.10. AhR+/+/ AhR - / - / si-Socs3 ARPE-19細胞在B [a] P處理下的IL-6蛋白變化 33 3.11. AhR+/+/ AhR - / - / si-Socs3 ARPE-19細胞在B[a]P處理下的TGF-beta表現 34 第四章 討論 35 4.1 B[a]P對發炎因子的影響 36 4.2 AhR和Socs3之關聯性 38 4.3 Socs3表現量上升與其生理意義之探討 39 4.4 AhR和Stat3的關聯性之探討 40 4.5 Stat3活化在RPE中的功能及與視網膜疾病之可能關聯 41 第五章 結論 43 參考文獻 45 圖表集 54 | |
| dc.language.iso | zh-TW | |
| dc.subject | 苯芘 | zh_TW |
| dc.subject | 眼睛 | zh_TW |
| dc.subject | 視網膜病變 | zh_TW |
| dc.subject | retinopathy | en |
| dc.subject | B[a]P | en |
| dc.subject | ocular | en |
| dc.title | 苯芘對視網膜色素上皮細胞AhR / Stat3路徑所調控之Socs3角色探討 | zh_TW |
| dc.title | Studies On The Molecular Mechanism Of The
Benzo [a] pyrene –Induced Socs3 Expression Via AhR / Stat3 Pathway In ARPE-19 Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭哲志,鄭幼文 | |
| dc.subject.keyword | 眼睛,視網膜病變,苯芘, | zh_TW |
| dc.subject.keyword | ocular,retinopathy,B[a]P, | en |
| dc.relation.page | 77 | |
| dc.identifier.doi | 10.6342/NTU201801403 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-07-16 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
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