Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/20175
標題: 在 Ramos B 細胞株中類鐸受體 7 接合子誘發細胞自噬及其對 B 細胞抗原接受器造成之細胞凋亡影響之研究
Toll-like Receptor 7 Ligands Induce Autophagy and Their Effects on B cell Antigen Receptor Mediated Apoptosis in Ramos B cells
作者: 樂以梅
Yueh, Yi-Mei
關鍵字: autophagy
細胞自噬
Toll-like receptor (TLR)
B cell antigen receptor (BCR)
類鐸受體
B 細胞抗原接受器
出版社: 生物醫學研究所
引用: Adams, J. M. & Cory, S. (2007). The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 26, 1324-1337. Akira S, Takeda K. (2004). Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499-511. Antonsson, B., S. Montessuit, et al. (2000). Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem. J. 345, 271-278. Arbour, N., J. L. Vanderluit, et al. (2008). Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. J. Neurosci. 28, 6068-6078. Baehrecke, E. H. (2005). Autophagy: dual roles in life and death? Nature Rev. Mol. Cell Biol. 6, 505-510. Baruch J. Toledano, Yolande Bastien, Francisco Noya, Sylvain Baruchel, and Bruce Mazer. (1997). Platelet-Activating Factor Abrogates Apoptosis Induced Cross-linking of the Surface IgM Receptor in a Human Lymphoblastoid Cell Line. The Journal of Immunology. 158, 3705-5. Bernales S, McDonald K, Walter P. (2006). Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS. Biol. 4, e423. Bishop GA, Ramirez LM, Baccam M et al. (2001). The immune response modifier resiquimod mimics CD40-induced B cell activation. Cell Immunol. 208, 9-17. Burkitt, D.A. (1958). A sarcoma involving the jaws in African children. Brit. J. Surg. 45, 218-223. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK et al. (2008). A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 456: 259-263. Caro LH, Plomp PJ, Wolvetang EJ, Kerkhof C, Meijer AJ. (1988). 3-Methyladenine, an inhibitor of autophagy, has multiple effects on metabolism. Eur. J. Biochem. 175, 325-329. Choi, M.S., Boise, L.H., et al. (1995). The role of bcl-XL in CD40-mediated rescue from anti-mu-induced apoptosis in WEHI-231 B lymphoma cells. Eur. J. Immunol. 25, 1352-1357. Cuervo AM, et al. (2004). Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 305, 1292-1295. Danial, N. N. & Korsmeyer, S. J. (2004). Cell death: critical control points. Cell. 116, 205-219. D''Amours, D., F.R. Sallmann, et al. (2001). Gain-of-function of poly ( ADP-ribose ) polymerase-1 upon cleavage by apoptotic proteases: implication for apoptosis. J. Cell Sci. 114, 3771-3778. Delgado MA, Elmaoued RA, Davis AS, Kyei G, Deretic V. (2008). Toll-like receptors control autophagy. EMBO J. 27, 1110-1121. Ding WX, Ni HM, Gao W, Hou YF, Melan MA, Chen X et al. (2007). Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J. Biol. Chem. 282, 4702-4710. Eisenberg-Lerner, A., Bialik, S., Simon, H.U., and Kimchi, A. (2009). Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 16, 966-975. Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M et al. (2006). Autophagy is involved in T cell death after binding of HIV envelope proteins to CXCR4. J. Clin. Invest. 116, 2161. Evens, A.M., and Gordon, L.I. (2002). Burkitt''s and Burkitt-like lymphoma. Curr. Treat Options Oncol. 3: 291-305. Feng Z, Zhang H, Levine AJ, Jin S. (2005). The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. USA. 102, 8204-8209. Fillatreau S, Gray D, and Anderton SM. (2008). Not always the bad guys: B cells as regulators of autoimmune pathology. Nat. Rev. Immunol. 8, 391-397. Galonek, H. L. & Hardwick, J. M. (2006). Upgrading the BCL-2 network. Nature Cell Biol. 8, 1317-1319. Green, D. R. (2005). Apoptotic pathways: ten minutes to dead. Cell. 121, 671-674. Gururajan M, Jacob J, Pulendran B. (2007). Toll-Like Receptor Expression and Responsiveness of Distinct Murine Splenic and Mucosal B-Cell Subsets. PLoS One. 2, e863. Hiroaki Niiro and Edward A. Clark. (2002). Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2, 945-956. Inbal B, Bialik S, Sabanay I, Shani G, Kimchi A. (2002). DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J. Cell Biol. 157, 455-468. Ito H, Daido S, Kanzawa T, Kondo S, Kondo Y. (2005). Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int. J. Oncol. 26, 1401-1410. Iwaki T, Iwaki A, Fukumaki Y, Tateishi J. (1995). αB-Crystallin in C6 glioma cells supports their survival in elevated extracellular K+: the implication of a protective role of αB-crystallin accumulation in reactive glia. Brain Res. 673, 47-52. Iwasaki A. and Medzhitov R. (2004). Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5, 987-995. Kamada, S., A. Shimono, et al. (1995). Bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. Cancer Res. 55, 354-359. Kaushik S, Massey AC, Mizushima N, & Cuervo AM. (2008). Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy. Mol .Biol. Cell. 19,2179-192. Kelsoe Garnett. (2000). Studies of the humoral immune reponse. .Immunologic Research. 22, 199-210. Klionsky, D., et al. (2008). Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4, 1-25. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H et al. (2007). ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ. 14, 230-239. Krammer, P. H. (2000). CD95's deadly mission in the immune system. Nature. 407, 789-795. Krieg A M, Yi A K, Matson S, Waldschmidt T J, Bishop G A, Teasdale R, Koretzky G A and Klinman D M. (1995). CpG motifs in bacterial DNA trigger direct B-cell activation. Nature. 374, 546-549. Kroemer, G. et al. (2005). Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 12 (Suppl. 2), 1463-1467. Kroemer, G., Galluzzi, L. and Brenner, C. (2007). Mitochondrial membrane permeabilization in cell death. Physiol. Rev. 87, 99-163. Kuss, A.W., Knodel, M., et al. (1999). A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti-IgM-induced cell death. Eur. J. Immunol. 29, 3077-3088. Lacarrubba, F., M.R. Nasca, and G. Micali. (2008). Advances in the use of topical imiquimod to treat dermatologic disorders. Ther. Clin. Risk Manag. 4, 87-97. Leon Su and Michael David. (1999). Inhibition of B Cell Receptor-Mediated Apoptosis by IFN. J. Immunol. 162, 6317-6321. Levine, B. & Yuan, J. (2005). Autophagy in cell death: an innocent convict? J. Clin. Invest. 115, 2679-2688. Li J., Ni M., Lee B., Barron E., Hinton D.R. and Lee A.S. (2008). The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells. Cell Death Differ. 15, 1460-1471. Lum, J. J, DeBerardinis, R. J. & Thompson, C. B. (2005). Autophagy in metazoans: cell survival in the land of plenty. Nature Rev. Mol. Cell Biol. 6, 439-448. M. P. Schön & M. Schön. (2004). Immune modulation and apoptosis induction: Two sides of the antitumoral activity of imiquimod. Apoptosis. 9, 291-298. Maiuri MC, Zalckvar E, Kimchi A, & Kroemer G. (2007). Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8,741-752. Marshak-Rothstein A. (2006). Toll-like receptors in systemic autoimmune disease. Nat. Rev. Immunol. 6, 823-835. Miller BC, Zhao Z, Stephenson LM, Cadwell K, Pua HH, Lee HK et al. (2008). The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy. 4: 309-314. Miller, R.L., et al. (1999). Imiquimod applied topically: a novel immune response modifier and new class of drug. Int. J. Immunopharmacol. 21, 1-14. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. (2008). Autophagy fights disease through cellular self-digestion. Nature. 451, 1069-1075. Nakayama, K., I. Negishi, et al. (1994). Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease, and lymphocttopenia. Proc. Natl. Acad. Sci. U S A. 91, 3700-3704. Nakayama J, Ohtsuki M, & Oda T. (2007). Caspase-independent cell death by Fas ligation in human thymus-derived T cell line, HPB-ALL cells. Microbiol Immunol. 51, 1029-1037. Niiro, H., and E. A. Clark. (2002). Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2, 945-956. Onda, M. (2009). Reducing the immunogenicity of protein therapeutics. Curr. Drug Targets. 10, 131-139. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E et al. (2001). A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res. 61, 439-444. Parker, D. C. (1993). T cell-dependent B cell activation. Annu. Rev. Immunol. 11, 331-360. Pattingre S, Bauvy C, Carpentier S, Levade T, Levine B, Codogno P. (2008). Role of JNK1-dependent Bcl-2 phosphorylation in ceramide induced macroautophagy. J. Biol. Chem. 284, 2719-2728. Pua HH, He YW. (2007). Maintaining T lymphocyte homeostasis: another duty of autophagy. Autophagy. 3: 266-267. Puthalakath, H. and A. Strasser. (2002). Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ. 9, 505-512. Rubinsztein, D. C., Gestwicki, J. E., Murphy, L. O. & Klionsky, D. J. (2007). Potential therapeutic applications of autophagy. Nature Rev. Drug Discov. 6, 304-312. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T et al. (2008). Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 456: 264-268. Saitoh T, Akira S. (2010). Regulation of innate immune responses by autophagy-related proteins. Journal of Cell Biology. 189, 925-935. Sarkar, S., Ravikumar, B., Floto, R.A., and Rubinsztein, D.C. (2009). Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 16, 46-56. Shintani, T. & Klionsky, D. J. (2004). Autophagy in health and disease: a double-edged sword. Science. 306, 990-995. Tanida, I., Ueno, T. & Kominami, E. (2004). LC3 conjugation system in mammalian autophagy. Int. J. Biochem. Cell Biol. 36, 2503-2518. Tasdemir E, Galluzzi L, Maiuri M C, Criollo A, Vitale I, Hangen E, Modjtahedi N, and Kroemer G. (2008). Methods for assessing autophagy and autophagic cell death. Methods Mol. Biol. 445, 29-76. Tatsuya Saitoh and Shizuo Akira. (2010). Regulation of innate immune responses by autophagy-related proteins. J Cell Biol. 189, 925-935. Thorburn, A. (2008). Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis. 13,1-9. Tinel, A. et al. (2007). Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and prosurvival NF-κB pathway. EMBO J. 26, 197-208. Tomai MA, Imbertson LM, Stanczak TL et al. (2000). The immune response modifiers imiquimod and R-848 are potent activators of B lymphocytes. Cell Immunol. 203, 55-65. Tsong, T. Y. (1983). Voltage modulation of membrane permeability and energy utilization in cells. Biosci. Rep. 3, 487-505. Tyring, S. (2001). Imiquimod applied topically: A novel immune response modifier. Skin Therapy Lett. 6, 1-4. Uematsu S, Akira S. (2006). Toll-like receptors and innate immunity. J. Mol. Med. 84, 712-725. Vaux, D. L., S. Cory, et al. (1988). Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 335, 440-442. Vousden, K. H. & Lane, D. P. (2007). p53 in health and disease. Nature Rev. Mol. Cell Biol. 8, 275-283. Wang, J. H. and Reinherz, E. L. (2002). Structural basis of T cell recognition of peptides bound to MHC molecules. Mol. Immonol. 38, 1039-1049. Watanabe K, Ichinose S, Hayashizaki K, Tsubata T. (2008). Induction of autophagy by B cell antigen receptor stimulation and its inhibition by costimulation. Biochem. Biophys. Res. Commun. 374, 274-281. Watanabe K, Tsubata T. (2009). Autophagy connects antigen receptor signaling to costimulatory signaling in B lymphocytes. Autophagy. 5, 108-110. Wu, Y. T., Tan, H. L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C. N., Codogno, P., and Shen, H. M. (2010). Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J. Biol. Chem. 285, 10850-10861. Xu Y, Jagannath C, Liu XD, Sharafkhaneh A, Kolodziejska KE, Eissa NT. (2007). Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27, 135-144. Yorimitsu T & Klionsky DJ. (2005). Autophagy: molecular machinery for self-eating. Cell Death Differ. 2, 1542-1552. Zheng, X., Y. Wang, et al. (2008). Bcl-xL is associated with the anti-apoptotic effector of IL-15 on the survival of CD65 (dim) natural killer cells. Mol. Immunol. 45, 2559-2569.
摘要: 細胞自噬 ( autophagy ) 在所有真核細胞中是為了細胞質恆定的高度保留的降解過程,而細胞自噬與細胞凋亡間的機能相關性是很複雜的。近來研究已經顯示細胞自噬對於先天免疫的調控很重要,並且類鐸受體 ( Toll-like receptor, TLR ) 接合子在巨噬細胞中能誘發細胞自噬。此外,類鐸受體接合子已經被證實在 B 細胞中能抑制消 B 細胞抗原接受器 ( B cell antigen receptor, BCR ) 活化所誘發細胞凋亡的進行,此為抑制消除自體活化之 B 細胞的重要機制。然而,在 B 細胞中類鐸受體接合子是否能誘發細胞自噬,及類鐸受體接合子誘發細胞自噬對 B 細胞抗原接受器活化誘發之細胞凋亡之生物意義還是未知。在此研究中,我們發現兩種人工合成的類鐸受體 7 接合子:Imiquimod 和 Resiquimod,皆可誘發 Ramos B細胞株的細胞自噬。此外,在 Ramos B 細胞株中 Imiquimod 與 Resiquimod 誘發的細胞自噬能拯救透過anti-IgM μ-chain抗體與 B 細胞抗原接受器結合引發的細胞凋亡,而且當細胞自噬藉由藥物 3-MA 或 Bafilomycin A1 抑制後消除了這個保護效果。這個結果不但闡明類鐸受體接合子及其所誘發之細胞自噬在 B 細胞抗原接受器活化誘發凋亡所扮演的角色,也讓我們能更深入的檢視自體免疫疾病的可能發生機制,亦希望能由此機制為基礎在未來發展出可能的預防及治療方式。
Autophagy is a highly conserved degradative process for cellular maintenance in all eukaryotic cells and its functional relationship with apoptosis is complex. Recent studies have shown that autophagy is important for the regulation of innate immunity and Toll-like receptor ( TLR ) ligands are potent autophagy inducers in macrophage. In addition, TLR ligands have been demonstrated to protect B cells from B cell antigen receptor ( BCR ) mediated apoptosis, an important mechanism to eliminate the autoreactive B cells. However, whether the TLR ligands could induce the autophagy in B cells and the biological significance of TLR induced autophagy in BCR mediated apoptosis is still unknown. In this study, we found that Imiquimod and Resiquimod, two synthetic TLR7 ligands, could induce autophagy in Ramos B cells. Moreover, Imiquimod and Resiquimod induced autophagy could rescue BCR mediated apoptosis via cross-linking with anti-IgM μ-chain antibodies in Ramos B cells and this protect effect was disrupted when autophagy was inhibited by 3-MA or Bafilomycin A1. These results not only presented a model for TLR-induced autophagy in BCR mediated apoptosis but also provided insight into the pathogenesis of autoimmune disease and a way of developing novel therapies.
URI: http://hdl.handle.net/11455/20175
其他識別: U0005-1808201113413500
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1808201113413500
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