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研究生: 黃幸怡
論文名稱: 去氫表雄固醇對老鼠體內製造腫瘤壞死因子-alfa及轉型生長素-beta的調節
An in vivo regulatory role of dehydroepiandrosterone in murine TNF-alfa and TGF-beta production
指導教授: 曾哲明
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
畢業學年度: 87
語文別: 中文
論文頁數: 65
中文關鍵詞: 去氫表雄固醇腫瘤壞死因子-alfa轉型生長素-beta
英文關鍵詞: dehydroepiandrosterone, TNF-alfa, TGF-beta
論文種類: 學術論文
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  • 去氫表雄固醇 (DHEA)是腎上腺皮質所分泌的類固醇荷爾蒙,是製造性荷爾蒙的中間產物,在哺乳動物體內參與多種生理作用,具有調節免疫反應的功能。本實驗室先前曾以離體狀態,研究DHEA對老鼠免疫細胞製造腫瘤壞死因子 (TNF-alfa) 及轉型生長素 (TGF-beta) 的影響,發現DHEA能促進P388D1細胞及腹腔巨噬細胞製造TNF-alfa 及 TGF-beta。本研究則延續前人研究結果,欲知老鼠施打DHEA後,對體內免疫細胞製造TNF- alfa及TGF- beta的功能,是否造成影響。Balb/c老鼠皮下施打DHEA 72 小時之後,採取血清並取出腹腔巨噬細胞,腹腔巨噬細胞以酯多醣(LPS)刺激活化,培養特定時間後,收集培養基上清液並以酵素免疫分析法測定培養基上清液及血清中TNF- alfa 及TGF-beta 的濃度。結果顯示,細胞在離體培養下,TNF- alfa 的分泌量在6小時達到最高峰,而老鼠施打每克重50ug及100ug的DHEA,其腹腔巨噬細胞分泌TNF- alfa 的能力顯著增加,但高於100ug 之劑量後,TNF- alfa 的分泌量即回復至控制組的水準。本實驗也以RT-PCR確認DHEA對TNF- alfa 的影響,結果顯示DHEA可促進老鼠腹腔巨噬細胞TNF- alfa 基因的表現。採取施打DHEA老鼠之血清,化驗結果顯示,DHEA不顯著影響血清中TNF-alfa 的濃度。由施打DHEA的老鼠身上分離之腹腔巨噬細胞,進行離體培養24小時後,無論施打何種劑量,其分泌TGF-beta 的能力均與控制組無顯著差異。採取施打DHEA老鼠的血清進行化驗,發現老鼠施打每克重100ug的DHEA時,血液中TGF-beta的濃度顯著低於控制組。dexamethasone是一種很強的免疫抑制劑,由施打dexamethasone的老鼠身上分離之腹腔巨噬細胞,進行離體培養6小時,其分泌TNF-alfa的能力顯著降低,不過如果同時施打dexamethasone及DHEA,則DHEA會對dexamethasone產生拮抗作用,即減少dexamethasone對巨噬細胞功能的抑制能力。分析血清中TNF-alfa 的含量,雖然dexamethasone的抑制效果不明顯,但是同時施打DHEA時,仍對dexamethasone的作用有影響。反之,dexamethasone顯著促進血清中TGF-beta 的濃度,然而DHEA無法拮抗dexamethasone對血清中TGF-beta濃度的促進作用。由本研究結果推知,施打DHEA對腹腔巨噬細胞分泌TNF-alfa的能力有顯著的促進作用,對血清中TGF- 的濃度有抑制作用。但在活體內,DHEA對分泌此兩種細胞激素的影響可能受到其他因素的干擾以致TNF-alfa的血清濃度 及腹腔巨噬細胞分泌TGF- beta的能力未因為施打DHEA而改變 ; 此外,dexamethasone及DHEA雖然同為固醇類荷爾蒙,但是DHEA可拮抗dexamethasone對TNF-alfa 的抑制效應。

    Dehydroepiandrosterone (DHEA) is a predominant androgen secreted by adrenal cortex. DHEA has been proposed to play an important role in regulating physiological and immunological system in mammals. Our previous report suggested that DHEA caused an enhancement in TNF-alfa and TGF-beta production by both P388D1 cells and peritoneal macrophage under in vitro condition. The specific aim of present study is to investigate whether DHEA have ability to regulate TNF-alfa and TGF-beta production under in vivo condition. Balb/c mice administrated DHEA subcutaneously were sacrificed at 72 hrs after the treatment, then the serum and peritoneal macrophages were collected. The peritoneal macrophages were cultured with LPS for a period of time and the supernatant was then collected. Both TNF-alfa and TGF-b concentration were quantified using ELISA kits. Results suggested that the TNF-alfa secretion by peritoneal macrophages from the mice injected with 50 ug per g body weight and 100 ug per g body weight of DHEA were significantly increased and reached peak 6 hr after incubation. However, the amount of TNF-alfa secretion by macrophages returned to control level when the dose higher than 100 ug per g body weight was given. Result from RT-PCR analysis confirmed the finding that expression of TNF-alfa mRNA was enhanced by in vivo administration of DHEA. By contrast, the serum level of TNF-alfa was not significantly affected by the drug treatment. The TGF-beta secretion by peritoneal macrophages under in vitro culture did not show a significant difference from mice receiving carrier (100 % ethanol). However, the serum level of TGF-beta of mice injected with 100 ug per g body weight of DHEA was significantly lower than the mice received carrier. Dexamethasone is a potent immunosuppressor. Mice injected 1ug per g body weight of dexamethasone showed a significant reduction in TNF-alfa secretion by peritoneal macrophages. However, injection of DHEA together with dexamethasone could overcome the immunosupressive effect of dexamethasone on TNF-alfa secretion. The serum level of TNF-alfa did not show a significant change in dexamethasone treated mice but it showed a significantly increase in the mice received both DHEA and dexamethasone. Mice received dexamethasone showed a significant increase in the serum level of TGF-beta. However, DHEA could not antagonize the augmented effect of dexamethasone on the serum level of TGF-beta. In conclusion, mice injected DHEA potentiated the TNF-alfa production by peritoneal macrophages but decreased the serum level of TGF-beta. Since the effect of DHEA on both TNF-alfa and TGF-beta production might be interfered by other factors under in vivo condition, the effect of DHEA on the serum level of TNF-alfa and the TGF-beta was not significant. In addition, DHEA might be an effective antagonist to overcome the suppressive effect of dexamethasone on TNF-alfa secretion in vivo.

    目錄 中文摘要………………………………………………………………………i 英文摘要………………………………………………………………………iii 圖次……………………………………………………………………………v 表次…………………………………………………………………… … … vi 壹、 前言……………………………………………………………………1 Ⅰ.文獻探討…………………………………………………………… …1 Ⅱ.待答問題…………………………………………………………… … 9 貳、 實驗材料與方法………………………………………………………10 一、試劑、抗體及藥品……………………………………………… …10 1.動物注射藥劑………………………………………………………… 10 2. 離體培養活化劑…………………………………………………… 10 3.酵素免疫分析法所需抗體與溶液………………………………… 10 4.抽取cDNA所需試劑………………………………………………… 12 5.反轉錄反應所需試劑……………………………………………… 12 6.聚合酵素鏈反應所需試劑 ………………………………… 13 二、細胞培養液…………………………………………………… 14 三、實驗動物……………………………………………………… 14 四、細胞的計數……………………………………………………… 15 五、動物的處理…………………………………………………… 15 六、分離老鼠腹腔巨噬細胞……………………………………… 16 七、腹腔巨噬細胞的培養………………………………………… 16 八、酵素免疫分析法………………………………………………… 16 1.TNF-a酵素免疫分法……………………………………………… 16 2. TGF-b酵素免疫分析法…………………………………………… 17 九、RNA的萃取…………………………………………………… 18 十、cDNA的備製…………………………………………………… 18 十一、聚合酵素鏈反應……………………………………………… 19 十二、統計分析方法………………………………………………… 19 參、 實驗結果…………………………………………………………… 21 一、 DHEA對老鼠分泌TNF-a及基因表現的影響……………… 21 二、 DHEA 對老鼠分泌TGF-b 的影響…………………………… 22 三、 DHEA與Dexamethasone交互作用對老鼠分泌TNF-a的影響…… 22 四、DHEA與Dexamethasone交互作用對老鼠分泌TGF-b的影響…… 23 肆、 討論………………………………………………………………………24 伍、參考文獻……………………………………………………………… 29 附錄一:圖片說明……………………………………………………………41 附錄二:表次……………………………………………………… 62

    Araghi, N. M., Z. Zhang, S. Jiang, O. Call, C. D. Eskelson and R. R .Watson. (1997). Cytokine dysregulation and increased oxidation is prevented by dehydroepiandrostrone in mice infected with murine leukemia retrovirus. Proc. Soc. Exp. Biol. Med. 216(3): 386.
    Ashkenazi, A., S. A. Marsters, and D. J. Capon. (1991). Protection against endotoxin shock by a tumor necrosis factor receptor immunoadhesin. Proc. Natl. Acad. Sci. USA 88 : 10535
    Barbara, J. AJ., X. van Ostade, and A. F. Lopez. (1996).Tumor necrosis factor-alpha (TNF-a): The good, the bad and potentially very effective. Immunol. Cell Biol. 74 : 434.
    Barrous, Z., P. Charru, and C. Lidy. (1997). Dehydroepiandrosterone (DHEA) and aging. Arch. Geronotol. Geriatrics 24 : 233.
    Ben-Nathan, D., B. Lachmi, S. Lustig, and G. Feuerstein. (1991). Protection of dehydroepiandrosterone (DHEA) in mice infected with viral encephalitis. Arch. Virol. 20 : 263.
    Beutler, B., and A. Cerami. (1988). Tumor necrosis, cachexia, shock, and inflammation : a common mediator. Ann. Rev. Biochem. 57 : 505.
    Blauer, K. L., M. Poth, W. M. Roger, and E. W. Bernton. (1991). Dehydroepiandrosterone antagonizes the suppressive effects of dexamethasone on lymphocyte proliferation. Endocrinoloy 129 : 3174.
    Bouaboula, M., P. Legoux, B. Pessegue, B. Delpech, X. Dumont, M. Piechaczyk, P. Casellas, and D. Shire. (1992). Quantitation of cytokine gene expression using a polymerase chain reaction method involving co-amplification with an internal multispecific control. J. Biol. Chem. 267 : 21830.
    Brockhaus, M., H. Schoenfeld, H. Schlaeger, W. Hunziker, W. Lesslauer, and H. Loetscher. (1990). Idetification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. Proc. Natl. Acad. Sci. USA 87: 3127.
    Brown, P., L.Wakefield, A. Levinson, and M. Sporn. (1990). Physicochmecial activation of recombinant latent transforming growth factor-beta's1, 2, 3. Growth Factor 3 : 35.
    Butenandt, A. and H. Dannenbaum. (1934). Isolierung eines neuen, physiologischen unwirksasmen Sterinderivates aus Mannerharn, seine Verknuepfung mit Dehydroandrosterone und Androsteron. Z. Physiol. Chem. 229 : 192.
    Carlestrom, K., S. Eriksson, and C. Rannevik. (1986). Sex steroid and steroid binding protein in female alcoholic liver disease. Acta. Endocrinol. ( Copenli) 111: 75.
    Coffman, R. L., D. A. Lebman, and B. Shrader. (1989). Transforming growth factor b specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J. Exp. Med. 170: 1039.
    Cooper, D. A., M. Duckett, V. Petts, and R. Penny. (1979). Corticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen stimulated human lymphocytes. Clin. Exp. Immunol. 37 : 145.
    Currie, G. A., and C. Basham,. (1975). Activated macrophages release a factor which lyses malignant cells but not normal cells. J. Exp. Med. 142 : 1600.
    Danenberg, H. D., G. Alpert, S. Lustig, and D. Ben-Nathan. (1992). Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production. Microbiol. Agent Chemother. 36 : 2275.

    Danielpour, D., and Sporn, M. B. (1990). Differential inhibition of transforming growth factor β1 and β2 activity by α2-macroglobulin. J. Biol. Chem. 265 : 6973.
    Daynes, R. A., and B. A. Araneo. (1989). Contrasting effects of glucocorticoids on the capatity of T cells to produce the growth factors interleukine-2 and interleukin-4. Eur. J. Immunol. 19 : 2319.
    Daynes, R. A., D. J. Dudiay. and B. A. Araneo. (1990). Regulation of murine lymphokine production in vivo : II. Dehydroepiandrosterone is a natural enhancer of interleukin 2 synthesis by helper T cells. Eur. J. Immunol. 20 : 793.
    Delpedro, A. D., M. J. Barjavel, Z. Mamdouh, and O. Bakouche. (1998). Activation of Human Monocytes by LPS and DHEA. J. Interferon Cytokine Res. 18 : 125.
    Dentener, M. A., V. Bazil, E. J. Von Asmuth, M. Ceska, and W. A. Buuman. (1993). Involvement of CD14 in lipopolysaccharide - induced TNF-a , IL-6 and IL-8 release by human monocyte and alvedlar macrophages. J. Immunol. 150 : 2885.
    Deslypere, J., P. Verdonck, and L.Vermeulen. (1985). Fat tissue: a steroid reservoir and site of steroid metabolism. J. Clin. Endocrinol. Metab. 61 : 561.
    De Peretti, E., and M.G. Forest. (1978). Pattern of plasma dehydroepiandrosterone sulfate levels in human from birth to adulthood : Evidence for testicular production. J. Clin. Endrocrinol. Metab. 47 : 572.
    De Martin, R., B. Haendler, R. H. Warbinek, H. Gaugitsch, M. Wrann, H. Schluesener, J. M. Seifert, S. Bomder, K. Frei, A. Fontana, and E. Hofer. (1987) Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-b gene. EMBO. J. 6 : 3673.
    Derynck, R., J. A. Tarett, E.Y. Chen, D. H. Eaton, J. R. Bell, R. K. Assoiun, A. B. Roberts, M. B. Sporn, and D. V. Goeddel. (1985). Human transforming growth factor-b complementary DNA sequence and expression in normal and transformed cells. Nature 316 : 701.
    Flaumenhaft, R., M. Abe, Y. Sato, K. Miyazono, J. Harpel, C. Heldin, and D. B. Rifkin. (1993). Role of the latent TGF-b by co-cultures of endothelial and smooth muscle cells. J. Cell. Biol. 120 : 995
    Fontana, A., K. Frei, S. Bodmer, E. Hofer, M. H. Schreier, M. A. Jr. Palladino, R. M. Zinkernagel. (1989). Transforming growth factor-b inhibits the generation of cytotoxic T cells in virus-infected mice. J. Immunol. 143 : 3230.
    Fontana, A., D. B. Constam, K. Frei, U. Malipiero, and H. W. Pfister. (1992).
    Modulation of the Immune Response by Transforming Growth Factor Beta. Int. Arch. Allergy. Immunol. 99 : 1
    Gerard, C., C. Bruyns, and A. Marchant. (1993). Interleukin-10 reduces the release of TNF-a and prevents lethality in experimental endotoxemia. J. Exp. Med. 177 : 547.
    Gordon, G. B., L. M. Shantz, and P. Talalay. (1987). Modulation of growth,
    differentiation, and carcinogenesis by dehydroepiandrosterone. Adv. Enzyme Regul. 26 : 355.
    Gordon, G. B., L. M. Shantz, and P. Talalay. (1988). Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand White rabbit with aortic intimal injury. J. Clin. Invert. 82 : 712.
    Gordon, G. B., L. Helz, K. J. Sover, and G. W. Comstock. (1993). Serum levels of DHEA and its sulfate, and the risk of developing bladder cancer. Cancer Res. 51 : 1366.
    Gordon, G. B., L. Helz, K. J. Sover, and G. W. Comstock. (1993). Serum levels of DHEA and its sulfate, and the risk of developing gastric cancer. Cancer Epidemiol. Biomatkers. Prev. 2 : 33.
    Grayson, J., N. J. Doolry, R. I. Koski, and R. M. Blaese. (1981). Immunoglobulin production induced in vitro by glucocorticoid hormon. J. Clin. Invest. 68 : 1539.
    Hadley, M. E. (1988). Adrenal steroids in Endocrinology Prentice-Hall International, Inc. New. Jersey. 349.
    Han, J., B. Beutler, and G. Huez. (1991). Complex regulation of TNF mRNA turn over in lipopolysaccharide - activated macrophages . Biochim. Biophsy. Acta. 1090 : 22.
    Hennebold, J. D., and R. A. Daynes. (1994). Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines. Endocrinology. 135 : 67.
    Hohmann, H. P., R. Remy, M. Brockhaus , A. P. Van Loon. (1989). Two different cell types have differfnt major receptors for human tumor necrosis factor (TNF-a). J. Biol. Chem. 264 : 1427.
    Jacokson, M. A., R. E. Fusaro, M. Galmarini, and W. Lang. (1991). Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in man with CD4 counts of 200-499. J. Infet. Dis. 164 : 864.
    James, K., N. Premchand, A. Skibinska, G. Skibinski, M. Nicol, and J. I. Mason. (1997). IL-6, DHEA and the aging process. Mechanisms of ageing and Development 93 : 15.
    Jue, D. M., B. Sherry, and C. Luedke. (1990). Processing of newly synthesized cachectin / tumor necrosis factor in endotoxin - stimulated macrophages . Biochemistry 29 : 8371.
    Kang, I. C., and H. C. Lee. (1996). Dehydroepiandrosterone and beta-endorphin enhance IL-12 gene expression. J. Korean. Soc. Microbiol. 31 : 399.
    Kehrl, J. H., A. B. Roberts, L. M. Wakefield, S. Jakowlew, M. B. Sporn, and A. S. Fauci. (1986). Transforming growth factor b is an important immunomodulatory protein for human B lymphocytes. J. Immunol. 137 : 3855.
    Komorowski, J., W. Jazdzyk, and H. Stepien. (1996). The mutual effect of Dehydroepiandrosterone and dexamethasone on Interleukin-8 release from human peripheral blood mononuclear cells culutred in vivo. Hormone Metab. Res. 28 : 570.
    Lane, S. J., J. R. W. Wilkinson, G. M. Cochrane, T. H. Lee, and J. P. Arm. (1993). Differential in vitro regulation by glucocorticoids of monocyte-derived cytokine generation in glucocorticoid-resistant bronchial asthma. Am. Rev. Respir. Dis. 147 : 690.
    Lee, G., R. Larry, L. R. Ellingsworth, S . Gillis, R. Wall, and P. W. Kincade. (1987). Transforming growth factors -b are potential reglulators of B lymphopoiesis. J. Exp. Med. 166 : 1290.
    Legoux, P., C. Minty, B. Delpech, A. J. Minty and D. Shire. (1992). Simultaneous quantitation of cytokine mRNAs in interleukin-1β stimulated U373 human astrocytoma cells by a polymerisation chain reaction method involving co-amplification with an internal multispecific control. Eur. Cytokine Network 3 : 553.
    Lucas, J. A., S. A. Ahmed, M.L. Cascy and P. C. Macdonald. (1985). Prevention of autoantibody formation and prolong survuval in New Zealand black / New Zealand white F1 mice fed dehydroepiandrosterone. J. Clin. Invest. 75 : 2091.
    Loria, R. M., T. H. Inge, S. Cook, A. K. Szakal, and W. Regelson. (1988). Protection against acute letheal viral infections with the native steroid (DHEA). J. Med Virol. 26 : 301.
    Loria, R. M., W. Regelson, and D. A. Padgett. (1990). Immune response facilitation and resistance to virus and bacterial infections with dehydroepiandrosterone (DHEA). In the biological role of DHEA. M. Kalimi and W. Regelson, eds. Walter De Gruyter, New York, p. 107.
    Lyons, R. M., L. E. Gentry, A. F. Purchio, and H. L. Moses. (1990). Mechanism of activation of latent recombinant transforming growth factor b1 by plasmin. J. cell Biol. 110 : 1361.
    Lyons, R. M., J. Keski-Oja, and H. L. Moses. (1988). Proteolytic activation of latent recombinant transforming growth factor b1 from fibroblast-conditioned medium. J. cell Biol. 106 : 1659.
    Loria, R. M., and D. A. Padgett. (1992). Mobilization of cutaneous immunity for systemic protection against infection. Ann. New York Acad. Sci. 650 : 363.
    Matine, D. W., P. A.Wayes, and V. W. Rodwell. (1983). Harpers review of biochemistry.494-497.
    Matthews, N. (1978). Tumor necrosis factor from the rabbit. Ⅱ. Production by monocytes. Br. J. cancer 38 : 310.
    Matthews, N. (1981). Production of an antitumor cytotoxin by human monocytes Immunology 44 : 135.
    Mclachlan, J. A., C. D. Serkin, and O. Bakouche. (1996). Dehydroepiandrosterone modulation of lipopolysaccharide-stimulated monocyte cytotoxicity. J. Immunol. 156 : 328.
    Meikle, A.W., R. A. Daynes, and B. A. Araneo. (1991). Adrenal androgen secretion and biologic effects. Endocrinol. Metab. Clin. N. Am. 20 : 396.
    Merril, C. R., M. G. Harrington, and T. Sunderland. (1990). Reduced plasma dehydroepiandrosterone concentrations in HIV infection and Alzheimer's disease. The biologic role of dehydroandrosterone (DHEA). M. Kalimi and W. Regelson, eds. Walter De Gruyter, New York,
    Miyazono, K., U. Hellman, C. Wernstedt, and C. Heldin. (1985). Latent high molecular weight complex of transforming growth factor b1. J. Biol. Chem. 263 : 6407.
    Miyazono, K., A. Olofsson, P. Colosetti, and C. Heldin. (1991). A role of latent TGF-b1 biding protein in the assembly and secretion of TGF- b 1. EMBO J. 10 : 1091.
    Padgett, D. A. and R. M. Loria. (1994). In vitro potentiation of lymphocyte activation by dehydroepiandrostrone, androstenediol, and androstenetriol. J. Immunol. 153 : 1544.
    Parker, L. N. (1991). Control of adreal adrogen secretion. Endocrinol. Metab. Clin. N. Am. 20 : 401.
    Pennica, D., J. S. Hayflck, T. S. Bringman, M. A. Palladino, and D. V. Goeddel. (1985) Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc. Natl. Acad. Sci. USA 83 : 6060.
    Reed, W.P. and Lucas, Z . J. (1975). Cytotoxic activity of lymphocytes V. role of souble toxin in macrophage-inhibited culuters of tumor cells. J. Immunol. 115 : 395.
    Renz, H., A. Henke, P. Hofmann, L. J. Wolff, A. Schmidt, J. Ruschoff, and D. Gemsa. (1992). Sensitization of rat alveolar macrophages to enhanced TNF-α release by in vivo treatment with dexamethasone. Cellular Immunology. 144 : 249.
    Regelson, W. R. Loria, and M. Kalimi. (1988). Hormonal intervention : " buffer hormones" or " state dependency" : the role of dehydroepiandrosterone (DHEA) , thyroid hormone , estrogen and hypophysectomy in aging. Ann. NY Acad. Sci. 521 : 260.
    Robel, P., & E-E. Bauliue. (1995). Dehydroepiandrosterone (DHEA) is a neuroactive neurosteroid. Ann. NY Acad. Sci. 774 : 82.
    Risdon, G., J. Cope, and M. Benett. (1990). Mechanisms of chemoprevention by dietary dehydroepiandrsterone. Am. J. Pathol. 136 : 759.
    Risdon, G., V. Kumar, and B. Bennett. (1991). Differential effects of dehydroepiandrsterone (DHEA) on murine lymphopoiesis and myelopoiesis. Exp. Hematol. 19 : 128.
    Roberts, G. (1990). Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) as neural facilitators: effects on brain tissue in culuter and on memory in young and old mice. A cyclic GMP hypothesis of action of DHEA and DHEAS in neurous system and other tissue. In the biological role of dehydroepiandrosterone (DHEA). M. Kalimi and W. Regelson eds. Walter de Gruyter. New York, p.13.
    Roberts, A. B., and M. B. Sporn. (1993). Physiological actions and clinical applications of transforming growth factor-beta (TGF-b). Growth factor 8 : 1.
    Ronald, F., G. E. van Vollenhoven , Engleman, and J. L. Mcguire (1995) Dehydroepiandrosterone in systemic lupus erythematosus. Arthritis Rheumatism 38 : 1826.
    Rom, W. N. and T. Harkin. (1990). Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophage in vitro in asbestosis. Environ. Res. 55 : 145.
    Santo, E. D., M. Sironi, T. Mennini, M. Zinetti, G. Savoldi, D. D. Lorenzo, and P. Ghezzi. (1996). A glucocorticoid receptor-independent mechanism for neurosteroid inhibition of tumor necrosis factor production. Eur. J. Pharmacol. 299 : 179.
    Saxon, A., R. H. Stevens, S. J. Ramer, P. J. Clements and T. Y. David. (1978). Glucocotiicoids administered in vivo inhibit human suppressor T lymphocyte function and dimish B lymphocyte responsiveness in vitro immunoglobulin synthesis. J. Clin. Invest. 61 : 922.
    Schinazi, R. F., B. F. Stevens, and S. J. Ramer. (1990). Effect of dehydroepiandrsterone in lymphocytes and Macrophages infected with human immunodeficiency viruses. The biologic role of dehydroisoandrosterone (DHEA). M. Kalimi and W. Regelson, eds. Walter de Gruyter. New York
    Sidhu, R. S., and A. P. Bollon. (1993). Tumor necrosis factor activities and cancer therapy-a perspective. Pharmacol. Therapeutics 57 : 79.
    Smith, R. A., and C. Baglioni. (1987) .The active form of tumor necrosis factor is a trimer. J. Biol Chem. 262 : 6951.
    Spencer, N. F. L., S. D. Norton, L. L. Harrison, G. Z. Li, and R. A. Daynes, (1996). Dysregulation of IL-10 production with aging: Possible linkage to the age-associated decline in DHEA and its sulfated derivative. Exp. Gerontol. 31(3) : 393.
    Suzuki, T., N. Suzuki, R. A. Daynes, and E. G. Engleman. (1991). Dehydroepiandrsterone enhances IL-2 production and cytotoxic effector function of human T cell. Clin. Immunol. Immunopath. 61 : 202.
    Szabo, G., P. Mandrekar, L. Girouard, and D. Catalano. (1996). Regulation of human monocyte functions by acute ethanol treatment: decreased tumor necrosis factor-alpha, interleukin-1 beta and elevated interleukin-10, and transforming growth factor-beta production. Aclcoholism Clin. Exp. Res. 20 : 900.
    Ten, D. P., P. Hansen, K. K. Iwata, C. Pieler, and J. G. Foulkes. (1988). Identification of another member of transforming growth factor type b gene family. Proc. Natl. Acad. Sci. USA 85 : 4715.
    Titus, R. G., B. Sherry, and A. Cerami. (1989). Tumor necrosis factor plays a protective role in experimental murine cutaneous Leishmaniasis. J. Exp. Med. 170 : 2097.
    Tracey, K. J., Y. Fong, D. G. Hesse. (1987). Anti-cachectin / TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330 : 662

    .
    Tracey, K. J., A. Cerami. (1994). Tumor necrosis factor : A pleiotropic cytokine and therapeutic target. Ann. Rev. Med. 45 : 491.
    Tseng, J., and C. J. Liou. (1994). Dehydroepiandrosterone regulates immunoglobulin A production of murine B lymphocytes. Int. J. Immunotherapy. 10 : 95.
    Vassalli, P. (1992). The pathophysiology of tumor necrosis factors. Ann. Rev. Immunol.10 : 411.
    Waage, A. and O. Bakke. (1988). Glucocorticoids supress the production of tumor necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology 63 : 299.
    Wahl, S. M., M. F. Nancy, and E. M. Stephan. (1989). Inflammatory and immunomodulatory roles of TGF-β. Immunol. Today. 10 : 258.
    Wu, M. F., H. L. Chang. and J. Tseng. (1997). Dehydroepiandrosterone induces the transforming growth factor-b production by murine macrophages. Int. J. Tiss. Reac. ⅩⅠⅩ(3/4)141.
    Yang, J. Y., A. Schwartz, and E. E. Henderson. (1993). Inhibition of HIV1-latency reactivation by dehydroepiandrosterone and an analog of DHEA. AIDS Res. human retroviruses 9 : 747.
    Zumoff, B., R. S. Rosenfeld, and G. W. Strain.(1980). Sex differences in the twenty-four-hour mean plasma concentrations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate(DHEAS) and the DHEA and DHEAS ratio in normal adult. J. Clin. Endocrinol. Metab. 51: 330.
    劉情君 1993 Regulatory role of dehydroepiandrosterone on B cell immunoglobulin production. 台灣師範大學碩士論文。
    吳美芬 1997 Dehydroepiandrosterone regulates the TNF-a and TGF-b production by murine immune cells. 台灣師範大學碩士論文。
    童褘珊 1998 In vitro study on the regulation of human immunoglobulin production by dehydroepiandrosterone (DHEA). 台灣師範大學碩士論文。

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