成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	李幸慧 Li, Hsing-hui
論文名稱：	介白素-20在腎臟疾病中的研究 Study of Interleukin-20 in Renal Diseases
指導教授：	張明熙 Chang, Ming-shi
學位類別：	博士 Doctor
系所名稱：	醫學院 - 基礎醫學研究所 Institute of Basic Medical Sciences
論文出版年：	2009
畢業學年度：	97
語文別：	英文
論文頁數：	95
中文關鍵詞：	介白素-20 、細胞激素、腎臟上皮細胞、急性腎衰竭、慢性腎臟病、狼瘡性腎炎、細胞凋亡、腎膈細胞
外文關鍵詞：	acute renal failure, lupus nephritis, chronic kidney disease, mesangial cells, renal epithelial cells, apoptosis, cytokines, interleukin-20
相關次數：	點閱：131 下載：2
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

介白素-20是一種新發現細胞激素，歸類為介白素-10家族細胞激素的成員。目前對於介白素-20的生物弁鄔猁齒陪迭C我們已經知道介白素-20與牛皮癬、類風濕性關節炎、粥狀動脈硬化等疾病有關。因此，我們想要去探討介白素-20是否與腎臟疾病有關，我們將探討三種與發炎相關的腎臟疾病，包含急性的腎臟疾病—急性腎衰竭、與慢性的腎臟疾病—慢性腎衰竭與狼瘡性腎炎。在急性腎衰竭的研究上，我們利用反轉錄聚合鏈鎖反應偵測基因的表現，發現介白素-20與其受體在急性腎衰竭的大鼠腎臟中，轉錄本表現量都會增加。我們利用免疫化學染色法偵測介白素-20的蛋白質表現，發現介白素-20在急性腎衰竭的大鼠腎臟近端小管上皮細胞中的表現量很高。因此，我們選用人類腎臟近端小管上皮細胞株(HK-2)作為後續試管內的研究。我們利用反轉錄聚合鏈鎖反應與細胞免疫化學染色法，證實HK-2細胞株表現介白素-20與其受體的轉錄本與蛋白質。接著，我們證實介白素-20會經由活化caspase 9造成HK-2細胞凋亡，且介白素-20也會活化與細胞凋亡相關的下游訊息傳導分子JNK 與 ERK 1/2。此外，介白素-20會使TGF-1轉錄本增加，而TGF-1是一個會造成腎臟損害的分子。當HK-2細胞在缺氧的狀態下，介白素-20與其受體介白素-22R1的轉錄本都會增加，而且，介白素-20會使IL-1的轉錄本增加。在動物實驗中，我們也證實了介白素-20的抗體會減少急性腎衰竭老鼠體內的TGF-1與 IL-1的蛋白質表現量，老鼠體內受損的腎小管面積也減少了。我們第一部份的研究顯示介白素-20會作用在腎臟上皮細胞，造成腎臟上皮細胞凋亡，而此過程與急性腎衰竭有著密切的關連。在第二部分的慢性腎衰竭研究上，我們首先發現第五期人類慢性腎臟疾病血清中表現較高的介白素-20。並且利用細胞免疫化學染色法證實介白素-20表現在慢性腎臟疾病老鼠的腎臟上皮細胞、腎膈細胞、和免疫細胞。除此之外，慢性腎臟疾病老鼠的肺臟、肝臟和心臟也有表現介白素-20。因此，我們同時也探討介白素-20在腎臟上皮細胞株的作用。結果，我們發現介白素-20會經由活化caspase 3導致腎臟上皮細胞凋亡。同時，介白素-20也會使間質纖維母細胞產生較多的TGF-1。因此，我們第二部份的研究顯示介白素-20會損害腎臟上皮細胞並導致腎臟上皮細胞凋亡，而且會使間質纖維母細胞產生較多的TGF-1加速慢性腎臟疾病的病程。最後，在第三部分的狼瘡性腎炎研究上，我們首先從全身性紅斑性狼瘡的老鼠腎臟分離出腎膈細胞，並且用正常老鼠的腎膈細胞作為對照組。我們發現介白素-20與其受體在全身性紅斑性狼瘡的老鼠的腎膈細胞中表現量比對照組高。而且，我們也證實介白素-20會刺激腎膈細胞產生MCP-1、RANTES、CXCL10、IL-6、iNOS、ROS並且活化ERK 1/2，這些分子都與狼瘡性腎炎的致病機轉有關。除此之外，我們也在臨床的檢體偵測到介白素-20表現在狼瘡性腎炎病人的腎膈細胞與發炎細胞中。我們第三部分的結果證實了介白素-20作用在腎膈細胞並且刺激腎膈細胞產生與狼瘡性腎炎的致病機轉有關的分子，證實介白素-20與狼瘡性腎炎相關。

IL-20 is a newly discovered proinflammatory cytokine belonging to IL-10 family. The present knowledge about IL-20 on inflammatory diseases is still limited. IL-20 was found to involve with psoriasis, rheumatic arthritis, and atherosclerosis. We want to investigate whether IL-20 is involved in the acute type renal diseases such as acute renal failure, or in chronic type renal diseases such as chronic kidney disease and lupus nephritis. In first part, acute renal failure, we analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl2-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20 and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF-1), a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1 transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-1, and IL-1and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure. In second part, CKD patients at stage ﬁve expressed signiﬁcantly higher IL-20 in serum than controls. Immunohistochemical staining demonstrated that more IL-20 protein was expressed in the kidney tubu¬lar-epithelial cells, mesangial cells, and immune cells of CKD rats with a 5/6 nephrectomy. The lung, liver, and heart tissue of CKD rats also overexpressed IL-20. Thus, we treated tubular epithelial cell line with IL-20 to study its effects on CKD. IL-20 treatment induced apoptosis in these cells via caspase 3 activation. Incubating IL-20 with rat interstitial ﬁbroblasts, NRK-49F cells, upregulated transforming growth factor (TGF)-1 production, one key inducer for renal ﬁbrogenesis. Therefore, IL-20 injured renal epithelial cells and induced ﬁbroblasts to produce TGF-1 that hastened the progression of CKD. Finally, we analyzed the expression of IL-20 and its receptors in mesangial cells derived from SLE–prone, NZB/W, and DBA/W mice. IL-20 and its receptors were upregulated in mesangial cells from NZB/W mice. Incubating IL-20 with mesangial cells upregulated the transcripts of MCP-1, RANTES, CXCL10, IL-6, iNOS, and ROS, all of which are involved in the pathogenesis of lupus nephritis. IL-20 specifically activated the downstream signal ERK 1/2. We also detected human IL-20 protein in both mesangial cells and inflammatory cells in kidney biopsies of patients with lupus nephritis. Our results reveal the novel effects of IL-20 on mesangial cells and its association with lupus nephritis.

中文摘要		I
Abstract	         III
誌謝	         V
Abbreviation List	VI
Table of Contents	VIII
List of Tables	XI
List of Figures	XII




I. Literature review	1
A. Interleukin (IL)-20 belonging to IL-10 family cytokines	1
B. Identification, cloning, and structure of IL-20	1
C. Receptors and signaling of IL-20	2
D. Expression of IL-20 and its receptor subunits	2
E. Biological function of IL-20	3
a. Role of IL-20 in psoriasis	3
b. Role of IL-20 in rheumatic arthritis (RA)	4
c. Role of IL-20 in atherosclerosis	5
d. Role of IL-20 in human intervertebral disc herniation	5
F. Acute renal failure	6
G. Chronic renal failure	7
H. Lupus nephritis	9
I. IL-10 and renal diseases	12
II. Rationale	13
III. Specific aims	15
A. To analyze the correlation of IL-20 with acute renal failure	15
B. To analyze the correlation of IL-20 with CKD	15
C. To analyze the correlation of IL-20 with lupus nephritis	15
IV. Material and methods	16
A. Study of IL-20 in acute renal failure	16
B. Study of IL-20 in chronic renal failure	21
C. Study of IL-20 in lupus nephritis	24
V. Results	29
A. Study of IL-20 in acute renal failure	29
a. Generating HgCl2-induced acute renal failure in rats	29
b. Transcript and protein levels of rat (r)IL-20 increased in the kidneys of rats
with HgCl2-induced acute renal failure	29
c. IL-20 and its receptors were expressed in human proximal tubular epithelial cells	30
d. IL-20 dose-dependently and specifically induced cell death in HK-2 cells	30
e. Human IL-20 induced mitochondria-dependent apoptosis and necrosis of HK-2 cells by activating caspase 9	31
f. IL-20 activated JNK and ERK 1/2 in HK-2 cells	32
g. IL-20 upregulated TGF-1 transcripts in normoxic HK-2 cells and upregulated IL-1 transcripts in hypoxic HK-2 cells	32
h. Hypoxia upregulated the transcripts of IL-20 and IL-22R1	33
i. Anti-hIL-20 monoclonal antibody protected rats with HgCl2-induced acute renal failure	33
B. Study of IL-20 in chronic renal failure	34
a. Higher levels of IL-20 in sera from stage 5 CKD patients	34
b. Generate animal model of chronic renal failure	34
c. Increased IL-20 was detected in kidney, liver, heart, and lung tissue of CKD rats	35
d. IL-20 induced apoptosis in mouse renal tubular epithelial cells	35
e. IL-20 induced rat interstitial fbroblasts to produce TGF-1	36
C. Study of IL-20 in lupus nephritis	37
a. Transcript levels of mIL-20 and its receptors were higher in the mesangial cells of NZB/W mice than in those of DBA/W control mice	37
b. Hypoxia induced mouse mesangial cells to produce IL-20	37
c. IL-20 induced mouse mesangial cells to produce chemokines and cytokines	38
d. IL-20 induced mouse mesangial cells to produce ROS and iNOS	38
e. IL-20 induced mouse mesangial cells to activate ERK1/2	39
f. Expression of IL-20 protein in the kidney tissue of patients with lupus nephritis	39
g. Expression of IL-20 in the spleen tissue of DBA/W and NZB/W mice	40
VI. Discussion	41
A. Study of IL-20 in acute renal failure	41
B. Study of IL-20 in CKD	44
C. Study of IL-20 in lupus nephritis.	47
D. The role of IL-20 in different diseases.	50
VII. Conclusion	51
VIII. References	52
IX. Tables	64
X. Figures and figure legends	67
XI. Publications	94
XII. Biographical note	95
                                    

1. Gesser B., Leffers H., Jinquan T., Vestergaard C., Kirstein N., Sindet-Pedersen S., Jensen S.L., Thestrup-Pedersen K., and Larsen C.G. Identification of functional domains on human interleukin 10. Proc Natl Acad Sci U S A 94: 14620-14625, 1997.
2. Pestka S., Krause C.D., Sarkar D., Walter M.R., Shi Y., and Fisher P.B. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22: 929-979, 2004.
3. Blumberg H., Conklin D., Xu W.F., Grossmann A., Brender T., Carollo S., Eagan M., Foster D., Haldeman B.A., Hammond A., Haugen H., Jelinek L., Kelly J.D., Madden K., Maurer M.F., Parrish-Novak J., Prunkard D., Sexson S., Sprecher C., Waggie K., West J., Whitmore T.E., Yao L., Kuechle M.K., Dale B.A., and Chandrasekher Y.A. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104: 9-19, 2001.
4. Zdanov A., Schalk-Hihi C., Gustchina A., Tsang M., Weatherbee J., and Wlodawer A. Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure 3: 591-601, 1995.
5. Hsieh M.Y., Chen W.Y., Jiang M.J., Cheng B.C., Huang T.Y., and Chang M.S. Interleukin-20 promotes angiogenesis in a direct and indirect manner. Genes Immun 7: 234-242, 2006.
6. Wei C.C., Hsu Y.H., Li H.H., Wang Y.C., Hsieh M.Y., Chen W.Y., Hsing C.H., and Chang M.S. IL-20: biological functions and clinical implications. J Biomed Sci 13: 601-612, 2006.
7. Dumoutier L., Leemans C., Lejeune D., Kotenko S.V., and Renauld J.C. Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol 167: 3545-3549, 2001.
8. Parrish-Novak J., Xu W., Brender T., Yao L., Jones C., West J., Brandt C., Jelinek L., Madden K., McKernan P.A., Foster D.C., Jaspers S., and Chandrasekher Y.A. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem 277: 47517-47523, 2002.
9. Hsu Y.H., Li H.H., Hsieh M.Y., Liu M.F., Huang K.Y., Chin L.S., Chen P.C., Cheng H.H., and Chang M.S. Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis. Arthritis Rheum 54: 2722-2733, 2006.
10. Nagalakshmi M.L., Murphy E., McClanahan T., and de Waal Malefyt R. Expression patterns of IL-10 ligand and receptor gene families provide leads for biological characterization. Int Immunopharmacol 4: 577-592, 2004.
11. Hsing C.H., Ho C.L., Chang L.Y., Lee Y.L., Chuang S.S., and Chang M.S. Tissue microarray analysis of interleukin-20 expression. Cytokine 35: 44-52, 2006.
12. Wolk K., Kunz S., Asadullah K., and Sabat R. Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol 168: 5397-5402, 2002.
13. Liu L., Ding C., Zeng W., Heuer J.G., Tetreault J.W., Noblitt T.W., Hangoc G., Cooper S., Brune K.A., Sharma G., Fox N., Rowlinson S.W., Rogers D.P., Witcher D.R., Lambooy P.K., Wroblewski V.J., Miller J.R., and Broxmeyer H.E. Selective enhancement of multipotential hematopoietic progenitors in vitro and in vivo by IL-20. Blood 102: 3206-3209, 2003.
14. Chen W.Y., Cheng B.C., Jiang M.J., Hsieh M.Y., and Chang M.S. IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 26: 2090-2095, 2006.
15. Wei C.C., Chen W.Y., Wang Y.C., Chen P.J., Lee J.Y., Wong T.W., Chen W.C., Wu J.C., Chen G.Y., Chang M.S., and Lin Y.C. Detection of IL-20 and its receptors on psoriatic skin. Clin Immunol 117: 65-72, 2005.
16. Romer J., Hasselager E., Norby P.L., Steiniche T., Thorn Clausen J., and Kragballe K. Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol. J Invest Dermatol 121: 1306-1311, 2003.
17. Gottlieb S.L., Gilleaudeau P., Johnson R., Estes L., Woodworth T.G., Gottlieb A.B., and Krueger J.G. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med 1: 442-447, 1995.
18. Nickoloff B.J., and Wrone-Smith T. Injection of pre-psoriatic skin with CD4+ T cells induces psoriasis. Am J Pathol 155: 145-158, 1999.
19. Li X., Fan X., Zhang K., Yin G., and Liu Y. Influence of psoriatic peripheral blood CD4+ T and CD8+ T lymphocytes on C-myc, Bcl-xL and Ki67 gene expression in keratinocytes. Eur J Dermatol 17: 392-396, 2007.
20. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 340: 115-126, 1999.
21. Heuze-Vourc'h N., Liu M., Dalwadi H., Baratelli F.E., Zhu L., Goodglick L., Pold M., Sharma S., Ramirez R.D., Shay J.W., Minna J.D., Strieter R.M., and Dubinett S.M. IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression. Biochem Biophys Res Commun 333: 470-475, 2005.
22. Deyo R.A., and Tsui-Wu Y.J. Descriptive epidemiology of low-back pain and its related medical care in the United States. Spine 12: 264-268, 1987.
23. Huang K.Y., Lin R.M., Chen W.Y., Lee C.L., Yan J.J., and Chang M.S. IL-20 may contribute to the pathogenesis of human intervertebral disc herniation. Spine 33: 2034-2040, 2008.
24. Schrier R.W., Wang W., Poole B., and Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest 114: 5-14, 2004.
25. Devarajan P. Cellular and molecular derangements in acute tubular necrosis. Curr Opin Pediatr 17: 193-199, 2005.
26. Rana A., Sathyanarayana P., and Lieberthal W. Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications. Apoptosis 6: 83-102, 2001.
27. Lieberthal W., Koh J.S., and Levine J.S. Necrosis and apoptosis in acute renal failure. Semin Nephrol 18: 505-518, 1998.
28. Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 17: 1503-1520, 2006.
29. Daha M.R., and van Kooten C. Is the proximal tubular cell a proinflammatory cell? Nephrol Dial Transplant 15 Suppl 6: 41-43, 2000.
30. Segerer S., Nelson P.J., and Schlondorff D. Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol 11: 152-176, 2000.
31. Bonventre J.V., and Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int 66: 480-485, 2004.
32. Simmons E.M., Himmelfarb J., Sezer M.T., Chertow G.M., Mehta R.L., Paganini E.P., Soroko S., Freedman S., Becker K., Spratt D., Shyr Y., and Ikizler T.A. Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney Int 65: 1357-1365, 2004.
33. Yamada T. [Studies on the mechanisms of renal damages induced by nephrotoxic compounds]. Nihon Hoigaku Zasshi 49: 447-457, 1995.
34. Liu X.Y., Jin T.Y., and Nordberg G.F. Increased urinary calcium and magnesium excretion in rats injected with mercuric chloride. Pharmacol Toxicol 68: 254-259, 1991.
35. Chaudhari A., and Kirschenbaum M.A. Alterations in rabbit renal microvascular prostanoid synthesis in acute renal failure. Am J Physiol 254: F684-688, 1988.
36. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39: S1-266, 2002.
37. Schoolwerth A.C., Engelgau M.M., Hostetter T.H., Rufo K.H., Chianchiano D., McClellan W.M., Warnock D.G., and Vinicor F. Chronic kidney disease: a public health problem that needs a public health action plan. Prev Chronic Dis 3: A57, 2006.
38. Eddy A.A. Progression in chronic kidney disease. Adv Chronic Kidney Dis 12: 353-365, 2005.
39. Meguid El Nahas A., and Bello A.K. Chronic kidney disease: the global challenge. Lancet 365: 331-340, 2005.
40. Reed J.C. Bcl-2 family proteins. Oncogene 17: 3225-3236, 1998.
41. Stahl P.J., and Felsen D. Transforming growth factor-beta, basement membrane, and epithelial-mesenchymal transdifferentiation: implications for fibrosis in kidney disease. Am J Pathol 159: 1187-1192, 2001.
42. Fleck C., Appenroth D., Jonas P., Koch M., Kundt G., Nizze H., and Stein G. Suitability of 5/6 nephrectomy (5/6NX) for the induction of interstitial renal fibrosis in rats--influence of sex, strain, and surgical procedure. Exp Toxicol Pathol 57: 195-205, 2006.
43. Morrison A.B., and Howard R.M. The functional capacity of hypertrophied nephrons. Effect of partial nephrectomy on the clearance of inulin and PAH in the rat. J Exp Med 123: 829-844, 1966.
44. Shimamura T., and Morrison A.B. A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am J Pathol 79: 95-106, 1975.
45. Rossmann P., Riha I., Matousovic K., Bohdanecka M., and Bukovsky A. Experimental ablation nephropathy. Fine structure, morphometry, cell membrane epitopes, glomerular polyanion and effect of subsequent transplantation. Pathol Res Pract 186: 491-506, 1990.
46. Kliem V., Johnson R.J., Alpers C.E., Yoshimura A., Couser W.G., Koch K.M., and Floege J. Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats. Kidney Int 49: 666-678, 1996.
47. Waldherr R., and Gretz N. Natural course of the development of histological lesions after 5/6 nephrectomy. Contrib Nephrol 60: 64-72, 1988.
48. Thomas G.L., Yang B., Wagner B.E., Savill J., and El Nahas A.M. Cellular apoptosis and proliferation in experimental renal fibrosis. Nephrol Dial Transplant 13: 2216-2226, 1998.
49. Zhang H., Wada J., Kanwar Y.S., Tsuchiyama Y., Hiragushi K., Hida K., Shikata K., and Makino H. Screening for genes up-regulated in 5/6 nephrectomized mouse kidney. Kidney Int 56: 549-558, 1999.
50. Malaviya A.N., Singh R.R., Kumar A., De A., Kumar A., and Aradhye S. Systemic lupus erythematosus in northern India: a review of 329 cases. J Assoc Physicians India 36: 476-480, 484, 1988.
51. Croker J.A., and Kimberly R.P. SLE: challenges and candidates in human disease. Trends Immunol 26: 580-586, 2005.
52. Singh R.R. SLE: translating lessons from model systems to human disease. Trends Immunol 26: 572-579, 2005.
53. Grande J.P. Mechanisms of progression of renal damage in lupus nephritis: pathogenesis of renal scarring. Lupus 7: 604-610, 1998.
54. Kuroiwa T., and Lee E.G. Cellular interactions in the pathogenesis of lupus nephritis: the role of T cells and macrophages in the amplification of the inflammatory process in the kidney. Lupus 7: 597-603, 1998.
55. Kuroiwa T. [Role of cytokine in the pathogenesis of lupus nephritis]. Nippon Rinsho 63 Suppl 5: 211-216, 2005.
56. Oates J.C., and Gilkeson G.S. Mediators of injury in lupus nephritis. Curr Opin Rheumatol 14: 498-503, 2002.
57. Ahsan H., Ali A., and Ali R. Oxygen free radicals and systemic autoimmunity. Clin Exp Immunol 131: 398-404, 2003.
58. Cooke M.S., Mistry N., Wood C., Herbert K.E., and Lunec J. Immunogenicity of DNA damaged by reactive oxygen species--implications for anti-DNA antibodies in lupus. Free Radic Biol Med 22: 151-159, 1997.
59. Ahmad J., Ashok B.T., and Ali R. Reactive oxygen species modified thymine and poly(dT) present unique epitope for human anti-DNA autoantibodies. Immunol Lett 58: 69-74, 1997.
60. Oates J.C., and Gilkeson G.S. The biology of nitric oxide and other reactive intermediates in systemic lupus erythematosus. Clin Immunol 121: 243-250, 2006.
61. Cattell V. Nitric oxide and glomerulonephritis. Semin Nephrol 19: 277-287, 1999.
62. Belmont H.M., Levartovsky D., Goel A., Amin A., Giorno R., Rediske J., Skovron M.L., and Abramson S.B. Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum 40: 1810-1816, 1997.
63. McCluskey R. Lupus nephritis. In: Kidney pathology decennial, edited by Sommers. New York: Appleton Century Crofts, 1975, p. 435-450.
64. Churg J., Bernstein J., and Glassock R.J. Lupus nephritis. In: Renal diseases: classification and atlas of glomerular diseases. Tokyo, Igaku-Shoin, 1995, p. 151-155.
65. Theofilopoulos A.N., and Dixon F.J. Murine models of systemic lupus erythematosus. Adv Immunol 37: 269-390, 1985.
66. Wakeland E.K., Wandstrat A.E., Liu K., and Morel L. Genetic dissection of systemic lupus erythematosus. Curr Opin Immunol 11: 701-707, 1999.
67. Ho A.S., and Moore K.W. Interleukin-10 and its receptor. Ther Immunol 1: 173-185, 1994.
68. Deng J., Kohda Y., Chiao H., Wang Y., Hu X., Hewitt S.M., Miyaji T., McLeroy P., Nibhanupudy B., Li S., and Star R.A. Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 60: 2118-2128, 2001.
69. Mu W., Ouyang X., Agarwal A., Zhang L., Long D.A., Cruz P.E., Roncal C.A., Glushakova O.Y., Chiodo V.A., Atkinson M.A., Hauswirth W.W., Flotte T.R., Rodriguez-Iturbe B., and Johnson R.J. IL-10 suppresses chemokines, inflammation, and fibrosis in a model of chronic renal disease. J Am Soc Nephrol 16: 3651-3660, 2005.
70. Moore K.W., de Waal Malefyt R., Coffman R.L., and O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19: 683-765, 2001.
71. Fouqueray B., Boutard V., Philippe C., Kornreich A., Marchant A., Perez J., Goldman M., and Baud L. Mesangial cell-derived interleukin-10 modulates mesangial cell response to lipopolysaccharide. Am J Pathol 147: 176-182, 1995.
72. Chadban S.J., Tesch G.H., Foti R., Atkins R.C., and Nikolic-Paterson D.J. Interleukin-10 is a mesangial cell growth factor in vitro and in vivo. Lab Invest 76: 619-627, 1997.
73. Houssiau F.A., Lefebvre C., Vanden Berghe M., Lambert M., Devogelaer J.P., and Renauld J.C. Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity. Lupus 4: 393-395, 1995.
74. Ishida H., Muchamuel T., Sakaguchi S., Andrade S., Menon S., and Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 179: 305-310, 1994.
75. Shevach E.M. CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2: 389-400, 2002.
76. Perez de Lema G., Maier H., Nieto E., Vielhauer V., Luckow B., Mampaso F., and Schlondorff D. Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. J Am Soc Nephrol 12: 1369-1382, 2001.
77. Ernest S., and Bello-Reuss E. Expression and function of P-glycoprotein in a mouse kidney cell line. Am J Physiol 269: C323-333, 1995.
78. Ka S.M., Cheng C.W., Shui H.A., Wu W.M., Chang D.M., Lin Y.C., and Chen A. Mesangial cells of lupus-prone mice are sensitive to chemokine production. Arthritis Res Ther 9: R67, 2007.
79. Okusa M.D. The inflammatory cascade in acute ischemic renal failure. Nephron 90: 133-138, 2002.
80. Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int 69: 213-217, 2006.
81. Abramson S.B., Dobro J., Eberle M.A., Benton M., Reibman J., Epstein H., Rapoport D.M., Belmont H.M., and Goldring R.M. Acute reversible hypoxemia in systemic lupus erythematosus. Ann Intern Med 114: 941-947, 1991.
82. Martinez-Taboada V.M., Blanco R., Armona J., Fernandez-Sueiro J.L., and Rodriguez-Valverde V. Acute reversible hypoxemia in systemic lupus erythematosus: a new syndrome or an index of disease activity? Lupus 4: 259-262, 1995.
83. Yuan Y., Hilliard G., Ferguson T., and Millhorn D.E. Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J Biol Chem 278: 15911-15916, 2003.
84. Lazzeri M. The physiological function of the urothelium--more than a simple barrier. Urol Int 76: 289-295, 2006.
85. Ghielli M., Verstrepen W., Nouwen E., and De Broe M.E. Regeneration processes in the kidney after acute injury: role of infiltrating cells. Exp Nephrol 6: 502-507, 1998.
86. Hsing C.H., Chiu C.J., Chang L.Y., Hsu C.C., and Chang M.S. IL-19 in involved in the pathogenesis of endotoxic shock. SHOCK 27: 2007.
87. Sauane M., Gopalkrishnan R.V., Sarkar D., Su Z.Z., Lebedeva I.V., Dent P., Pestka S., and Fisher P.B. MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev 14: 35-51, 2003.
88. Aggarwal S., Takada Y., Mhashilkar A.M., Sieger K., Chada S., and Aggarwal B.B. Melanoma differentiation-associated gene-7/IL-24 gene enhances NF-kappa B activation and suppresses apoptosis induced by TNF. J Immunol 173: 4368-4376, 2004.
89. Khan S., Cleveland R.P., Koch C.J., and Schelling J.R. Hypoxia induces renal tubular epithelial cell apoptosis in chronic renal disease. Lab Invest 79: 1089-1099, 1999.
90. Hauser P., and Oberbauer R. Tubular apoptosis in the pathophysiology of renal disease. Wien Klin Wochenschr 114: 671-677, 2002.
91. Miyazawa K., Suzuki K., Ikeda R., Moriyama M.T., Ueda Y., and Katsuda S. Apoptosis and its related genes in renal epithelial cells of the stone-forming rat. Urol Res 33: 31-38, 2005.
92. Edelstein C.L. What is the role of tubular epithelial cell apoptosis in polycystic kidney disease (PKD)? Cell Cycle 4: 1550-1554, 2005.
93. Kim Y.K., Kim H.J., Kwon C.H., Kim J.H., Woo J.S., Jung J.S., and Kim J.M. Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol 25: 374-382, 2005.
94. Zhuang S., Yan Y., Daubert R.A., Han J., and Schnellmann R.G. ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells. Am J Physiol Renal Physiol 292: F440-447, 2007.
95. Kunduzova O.R., Bianchi P., Pizzinat N., Escourrou G., Seguelas M.H., Parini A., and Cambon C. Regulation of JNK/ERK activation, cell apoptosis, and tissue regeneration by monoamine oxidases after renal ischemia-reperfusion. Faseb J 16: 1129-1131, 2002.
96. Hay E.D., and Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 26: 678-690, 1995.
97. Dai C., Yang J., and Liu Y. Transforming growth factor-beta1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling. J Biol Chem 278: 12537-12545, 2003.
98. Basile D.P., Rovak J.M., Martin D.R., and Hammerman M.R. Increased transforming growth factor-beta 1 expression in regenerating rat renal tubules following ischemic injury. Am J Physiol 270: F500-509, 1996.
99. Faubel S., Lewis E.C., Reznikov L., Ljubanovic D., Hoke T., Somerset H., Oh D.J., Lu L., Klein C., Dinarello C.A., and Edelstein C.L. Cisplatin-induced ARF is associated with an increase in the cytokines IL-1{beta},IL-18, IL-6 and neutrophil infiltration in the kidney. J Pharmacol Exp Ther 322: 8-15, 2007.
100. Otkjaer K., Kragballe K., Johansen C., Funding A.T., Just H., Jensen U.B., Sorensen L.G., Norby P.L., Clausen J.T., and Iversen L. IL-20 Gene Expression Is Induced by IL-1beta through Mitogen-Activated Protein Kinase and NF-kappaB-Dependent Mechanisms. J Invest Dermatol 2007.
101. Girardi G., and Elias M.M. Evidence for renal ischaemia as a cause of mercuric chloride nephrotoxicity. Arch Toxicol 69: 603-607, 1995.
102. Brezis M., and Epstein F.H. Cellular mechanisms of acute ischemic injury in the kidney. Annu Rev Med 44: 27-37, 1993.
103. Levin A. Clinical epidemiology of cardiovascular disease in chronic kidney disease prior to dialysis. Semin Dial 16: 101-105, 2003.
104. Yamamoto T., Noble N.A., Miller D.E., and Border W.A. Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. Kidney Int 45: 916-927, 1994.
105. Noris M., Bernasconi S., Casiraghi F., Sozzani S., Gotti E., Remuzzi G., and Mantovani A. Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis. Lab Invest 73: 804-809, 1995.
106. Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., and Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med 167: 332-344, 1988.
107. Malide D., Russo P., and Bendayan M. Presence of tumor necrosis factor alpha and interleukin-6 in renal mesangial cells of lupus nephritis patients. Hum Pathol 26: 558-564, 1995.
108. Lui S.L., Tsang R., Wong D., Chan K.W., Chan T.M., Fung P.C., and Lai K.N. Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice. Lupus 11: 411-418, 2002.

校內：立即公開
校外：2008-11-11公開

簡易檢索 / 詳目顯示

相關論文