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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49416完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉扶東(Fu-Tong Liu) | |
| dc.contributor.author | Yun-Hsi Huang | en |
| dc.contributor.author | 黃芸熙 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:27:41Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-17 | |
| dc.identifier.citation | 1. Zouboulis, C.C., Acne and sebaceous gland function. Clin Dermatol, 2004. 22(5): p. 360-6.
2. Schneider, M.R. and R. Paus, Sebocytes, multifaceted epithelial cells: lipid production and holocrine secretion. Int J Biochem Cell Biol, 2010. 42(2): p. 181-5. 3. Makrantonaki, E., R. Ganceviciene, and C. Zouboulis, An update on the role of the sebaceous gland in the pathogenesis of acne. Dermatoendocrinol, 2011. 3(1): p. 41-9. 4. Toth, B.I., et al., 'Sebocytes' makeup': novel mechanisms and concepts in the physiology of the human sebaceous glands. Pflugers Arch, 2011. 461(6): p. 593-606. 5. Yoon, J.Y., et al., Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes. J Invest Dermatol, 2013. 133(2): p. 429-40. 6. Li, Z.J., et al., Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes. J Invest Dermatol, 2014. 134(11): p. 2747-56. 7. Zouboulis, C.C., [The sebaceous gland]. Hautarzt, 2010. 61(6): p. 467-8, 4704, 476-7. 8. Jin, H., et al., Animal models of atopic dermatitis. J Invest Dermatol, 2009. 129(1): p. 31-40. 9. Thomsen, S.F., Atopic dermatitis: natural history, diagnosis, and treatment. ISRN Allergy, 2014. 2014: p. 354250. 10. Cookson, W., The immunogenetics of asthma and eczema: a new focus on the epithelium. Nat Rev Immunol, 2004. 4(12): p. 978-88. 11. Grosshans, E. and M. Woehl, [Abnormal vasomotor, sudoral and sebaceous reactions in atopic dermatitis (author's transl)]. Ann Dermatol Venereol, 1982. 109(2): p. 151-62. 12. Takigawa, H., et al., Deficient production of hexadecenoic acid in the skin is associated in part with the vulnerability of atopic dermatitis patients to colonization by Staphylococcus aureus. Dermatology, 2005. 211(3): p. 240-8. 13. Hiroyuki Araki, Y.S.a.H.T., Improvement of Atopic Dermatitis by Human Sebaceous Fatty Acids and Related Lipids, in Atopic Dermatitis - Disease Etiology and Clinical Management, J.E.-G.a.I. Dekio, Editor. 2012, InTech. 14. Wirth, H., M. Gloor, and D. Stoika, Sebaceous glands in uninvolved skin of patients suffering from atopic dermatitis. Arch Dermatol Res, 1981. 270(2): p. 167-9. 15. Cummings, R.D. and F.T. Liu, Galectins, in Essentials of Glycobiology, A. Varki, et al., Editors. 2009: Cold Spring Harbor (NY). 16. Rabinovich, G.A. and M.A. Toscano, Turning 'sweet' on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol, 2009. 9(5): p. 338-52. 17. Yang, R.Y., et al., Cell cycle regulation by galectin-12, a new member of the galectin superfamily. J Biol Chem, 2001. 276(23): p. 20252-60. 18. Harrison, W.J., et al., Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes. J Invest Dermatol, 2007. 127(6): p. 1309-17. 19. Yang, R.Y., et al., Galectin-12 is required for adipogenic signaling and adipocyte differentiation. J Biol Chem, 2004. 279(28): p. 29761-6. 20. Yang, R.Y., et al., Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice. Proc Natl Acad Sci U S A, 2011. 108(46): p. 18696-701. 21. Yang, R.Y., P.J. Havel, and F.T. Liu, Galectin-12: A protein associated with lipid droplets that regulates lipid metabolism and energy balance. Adipocyte, 2012. 1(2): p. 96-100. 22. Zouboulis, C.C., et al., Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95). J Invest Dermatol, 1999. 113(6): p. 1011-20. 23. Skehan, P., et al., New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst, 1990. 82(13): p. 1107-12. 24. Arikawa, J., et al., Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus. J Invest Dermatol, 2002. 119(2): p. 433-9. 25. Wille, J.J. and A. Kydonieus, Palmitoleic Acid Isomer (C16:1Δ6) in Human Skin Sebum Is Effective against Gram-Positive Bacteria. Skin Pharmacology and Physiology, 2003. 16(3): p. 176-187. 26. Nicolaou, A., et al., Polyunsaturated Fatty Acid-derived lipid mediators and T cell function. Front Immunol, 2014. 5: p. 75. 27. Calder, P.C., Polyunsaturated fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids, 2006. 75(3): p. 197-202. 28. Wang LF, L.J., Hsieh KH, Lin RH., <Epicutaneous exposure of protein antigen induces a predominant Th2-like response with high IgE production in mice.pdf>. J Immunol., 1996. 156(11): p. 4077-82. 29. Spergel JM, M.E., Brewer JP, Martin TR, Bhan AK, Geha RS., <Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice.pdf>. J Clin Invest., 1998. 101(8): p. 1614-22. 30. Gorjao, R., et al., Regulation of human lymphocyte proliferation by fatty acids. Cell Biochem Funct, 2007. 25(3): p. 305-15. 31. Pompéia C, L.L., Miyasaka CK, Procópio J, Sannomiya P, Curi R., Effect of fatty acids on leukocyte function. Braz J Med Biol Res., 2000. Nov;33(11):1255-68. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49416 | - |
| dc.description.abstract | 半乳糖凝集素-12(galectin-12)係一種可結合半乳糖苷(β-galactoside)的動物凝集素，具有兩個連結的碳水化合物識別區。它表現在脂肪細胞、白細胞、皮脂細胞且分布在細胞內的脂肪油滴周圍。先前文獻指出galectin-12在脂質代謝中扮演調控的角色。根據我們最近的研究，發現galectin-12藉由調控過氧化物酶體增殖物激活受體γ (peroxisome proliferator-activated receptor-γ)的基因表現而影響皮脂細胞的功能，包括皮脂細胞的分化、增生及脂質生成。此外，在galectin-12基因剔除小鼠中，發現皮脂腺的大小下降。研究也指出皮脂腺和多種皮膚疾病有關，包括異位性皮膚炎(atopic dermatitis，AD)。結合以上所述，我們假設galectin-12可能藉由調控皮脂細胞的功能，進而參與異位性皮膚炎的致病機轉。我們在galectin-12基因剔除小鼠中發現表皮厚度下降、由脾臟細胞製造的輔助型T細胞Th1及Th2 細胞激素的量有下降的趨勢，且這些激素的基因表現量，及肥大細胞的數目在皮膚病灶處也呈現下降現象。以上結果顯示當galectin-12缺失時，老鼠的發炎狀況較輕微，雖然我們觀察到Th2反應和OVA-specific IgE的量反而上升。接下來，我們進一步探討galectin-12在皮脂細胞的發炎反應中所扮演的角色。我們使用RNA干擾 (RNA interference)的方式抑制galectin-12的基因表現，再以脂多醣(LPS) 或痤瘡丙酸桿菌(Propionibacterium acnes) 刺激皮脂細胞，藉以探討galectin-12在皮脂細胞的發炎反應中所扮演的角色，並深入探討可能的機制。結果顯示當皮脂細胞中的galectin-12降低時，IL-1α, TNF-α, IL-6 and IL-8的mRNA表現量及分泌量皆下降。另外，當galectin-12下降時，p-IKKβ, p-IκB, IκB, total NFκB及NFκB移至細胞核的量也下降。綜合以上結果，我們認為galectin-12與AD有關，且在皮脂細胞的發炎反應中扮演調節性的角色。 | zh_TW |
| dc.description.abstract | Galectin-12 is a β-galactoside-binding animal lectin with two carbohydrate recognition domains (CRDs) and a linker sequence. It is expressed in adipocytes, leukocytes and sebocytes and associated with lipid droplets in cells. Previous studies suggested that galectin-12 plays a role in regulating lipid metabolism. Our recent study showed that galectin-12 is also involved in the regulation of sebocyte functions, including sebocyte differentiation, proliferation and lipogenesis by modulating peroxisome proliferator-activated receptor (PPAR)-γ expression. In addition, galectin-12-deficient mice showed a smaller size of sebaceous glands. It has been reported that sebaceous glands are associated with several skin diseases, including atopic dermatitis. Taken together, we hypothesized that galectin-12 may contribute to atopic dermatitis (AD) through regulating sebocyte functions. In AD model, we found a reduced epidermal thickness, slightly lower Th1 and Th2 cytokine production by splenocytes and mRNA expression in skin lesions, decreased numbers of mast cells in galectin-12-deficient mice, indicating the inflammatory status was alleviated in the absence of galectin-12, though the Th2 response and OVA-specific IgE were contradictory elevated. Next, we investigated the role of galectin-12 in regulating sebocyte inflammatory responses, using LPS or Propionibacterium acnes for stimulation after knockdown of galectin-12 by RNA interference and further addressed the underlying mechanism. Results supported that down-regulation of galectin-12 reduced IL-1α, TNF-α, IL-6 and IL-8 at mRNA and protein levels in SZ95 human sebocytes. Moreover, p-IKKβ, p-IκB, IκB, total NFκB levels, and translocation of NFκB to the nucleus were decreased when galectin-12 was down-regulated. We conclude that galectin-12 is involved in the development of AD and plays a regulatory role in the inflammatory responses of sebocytes. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:27:41Z (GMT). No. of bitstreams: 1 ntu-105-R03449005-1.pdf: 1527516 bytes, checksum: 8498a9108e3d459781221eb108912760 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | Abstract 1
中文摘要 3 Introduction 5 1. Sebaceous glands 5 1-1. Sebaceous glands in maintaining physiological skin barrier function 5 1-2. The role of sebocytes in skin inflammation and acnes 5 2. Atopic dermatitis 6 2-1. Introduction of atopic dermatitis 6 2-2. The role of sebaceous glands in atopic dermatitis 8 3. Galectins 8 3-1. Galectins 9 3-2. The functions of galectin-12 9 3-3. The role of galectin-12 in regulating sebocytes 10 Rationale 12 Experimental design 14 Materials and methods 16 1. Cell culture and reagents 16 2. Propionibacterium acnes culture and heat-inactivation 16 3. Generation of galectin-12 knockdown SZ95 cells by siRNA transfection 17 4. RNA Preparation, cDNA Synthesis, and Quantitative PCR 17 5. Sulforhodamine B (SRB) assay 18 6. Enzyme-linked immunosorbent assay (ELISA) 19 7. Western blot 19 8. Animals 20 8-1. Epicutaneous (EC) sensitization 21 8-2. Restimulation of splenocytes in vitro 21 8-3. Histology 22 8-4. Quantitation of IgG1, IgG2a and IgE in the serum and Th1 and Th2 cytokines secreted by splenocytes 22 8-5. RNA Preparation, cDNA Synthesis, and Quantitative PCR 23 8-6. Transepidermal water loss 23 9. Statistical analysis 23 Results 24 Part I. The role of galectin-12 in atopic dermatitis (AD) 24 1. Epidermal thickness at the OVA-sensitized skin sites 26 2. OVA-specific IgG1 and IgG2a levels in serum 26 3. OVA-specific IL-4, IL-5, IL-13 and IFN-γ secreted by splenocytes 27 4. mRNA expression of IL-4, IL-5, IL-13, IFN-γ and TSLP in OVA-sensitized skin sites 27 5. OVA-specific IgE in serum 28 6. Mast cells in OVA-treated skin sites 28 7. Transepidermal water loss (TEWL) 29 Part II. The involvement of galectin-12 in sebocyte inflammatory responses 29 1. Preparation of transient galectin-12 knockdown SZ95 cells. 29 2. Down-regulation of galectin-12 in LPS-induced human SZ95 sebocyte inhibits inflammatory cytokine levels 30 3. Down-regulation of galectin-12 in LPS-induced human SZ95 sebocyte reduces p-IKKβ, p-IκB, IκB, total NFκB, levels and translocation of NFκB to the nucleus. 31 Discussion 32 References 35 Figures 38 | |
| dc.language.iso | en | |
| dc.subject | 發炎 | zh_TW |
| dc.subject | 半乳糖凝集素-12 | zh_TW |
| dc.subject | 皮脂腺 | zh_TW |
| dc.subject | 皮脂細胞 | zh_TW |
| dc.subject | 異位性皮膚炎 | zh_TW |
| dc.subject | atopic dermatitis | en |
| dc.subject | Galectin-12 | en |
| dc.subject | inflammation | en |
| dc.subject | sebaceous glands | en |
| dc.subject | sebocytes | en |
| dc.title | 半乳糖凝集素-12於人類皮脂細胞發炎反應中所扮演的角色 | zh_TW |
| dc.title | The Role of Galectin-12 in Regulating Inflammatory Responses in Human Sebocytes | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林國儀(Kuo-I Lin),許秉寧(Ping-Ning Hsu) | |
| dc.subject.keyword | 半乳糖凝集素-12,皮脂腺,皮脂細胞,異位性皮膚炎,發炎, | zh_TW |
| dc.subject.keyword | Galectin-12,sebaceous glands,sebocytes,atopic dermatitis,inflammation, | en |
| dc.relation.page | 51 | |
| dc.identifier.doi | 10.6342/NTU201603087 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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