博碩士論文 100224017 詳細資訊




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姓名 陳慶戎(Ching-jung Chen)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 環狀核苷酸磷酸二酯酶4對LPS/TLR4訊息傳導誘導小鼠巨噬細胞表現IFN-β的影響
(Cyclic nucleotide phosphodiesterase 4 regulates LPS/TLR4 signaling-induced IFN-β expression in mouse macrophages)
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摘要(中) 干擾素-β(IFN-β)可促進多種干擾素刺激基因(IFN stimulated genes)表現,提高宿主的先天免疫能力。文獻指出,多種抗原結構如細菌表面結構lipopolysaccharide (LPS)會藉由活化細胞表面Toll-like receptor (TLR)的訊息傳導使IFN-β產生,而這些免疫反應多會受到cAMP的訊息傳導調控。環狀核苷酸磷酸二酯酶4 (phosphodiesterase 4;PDE4)是免疫細胞中主要水解cAMP的酵素,因此可有效調控細胞內cAMP的濃度。本研究主要是探討在巨噬細胞中PDE4是否參與IFN-β的產生及其作用機制。我們使用LPS處理Raw264.7巨噬細胞發現IFN-β的表現會隨著LPS處理濃度增加而上升,且在處理三小時達到最高。此IFN-β的表現會被PDE4抑制劑rolipram顯著抑制,其IC50約為0.115 µM。此rolipram的抑制作用是經由活化cAMP訊息傳導所致,因為以cAMP類似物dibutyryl cAMP處理Raw264.7細胞也有相同的抑制作用。進一步使用exchange-protein activated by cAMP (Epac)抑制劑ESI-09或protein kinase A (PKA)抑制劑Rp-8-CPT-cAMP處理細胞,結果顯示抑制Epac不會使rolipram對IFN-β的抑制作用回復,而抑制PKA可回復約57 %,同時,PKA活化劑6-Bnz-cAMP也可顯著抑制IFN-β表現,其抑制程度與rolipram相當,這表示rolipram可藉由活化cAMP/PKA訊息傳導來抑制IFN-β表現。為進一步了解PDE4亞型對IFN-β的調控,我們使用PDE4基因剔除小鼠之腹腔巨噬細胞進行實驗,結果顯示,去除PDE4B的細胞其LPS誘導IFN-β的表現呈現顯著下降,且rolipram不再進一步抑制此反應。相反的,PDE4A-/-與PDE4D-/-細胞其IFN-β表現與野生型巨噬細胞相當,且均會被rolipram顯著抑制。這些結果表示rolipram抑制IFN-β表現主要是藉由抑制PDE4B所致。此外,本研究進一步探討抑制PDE4是否會影響TRIF-dependent訊息傳導路徑,西方點墨法分析轉錄因子IRF3活化的結果顯示,在Raw264.7細胞內IRF3磷酸化作用會隨著LPS處理時間增加而上升,至三小時後有下降的趨勢,然而在三小時前rolipram對IRF3鄰酸化無顯著影響,僅至五小時才有顯著下降。再者,LPS可使IRF3的上游分子TBK1活化,但此TBK1磷酸化作用也不受rolipram調控。綜合上述結果證實,在巨噬細胞內抑制PDE4B可活化cAMP/PKA訊息傳導,進而抑制LPS誘導IFN-β mRNA表現,但這反應並非經由調控TLR4/TRIF/TBK1/IRF3訊息傳導路徑所致。
摘要(英) Interferon-β (IFN-β) is a crucial component of innate immune system which enhances IFN-stimulated genes (ISGs) expression to promote the host’s immunity. Numerous data indicated that various pathogenic structures, such as lipopolysaccharide (LPS), can up-regulate IFN-β production by activating toll like receptor (TLR) signal pathways. Many of these responses can be modulated by cAMP signaling. Type 4 cAMP-specific phosphodiesterases (PDE4s) are the predominant cAMP-hydrolyzing enzymes in most immune cells and, thereby important in modulating cAMP concentration in these cells. In this study, we aimed to determine whether PDE4 is involved in regulation of IFN-β production in mouse macrophages, and its underlying mechanisms. By stimulation of Raw264.7 macrophages with LPS, we found a dose-dependent increase in IFN-β mRNA expression and the IFN-β mRNA level reached maximum at 3 h after LPS treatment. The PDE4 inhibitor rolipram effectively suppressed the IFN-β expression with the IC50 of approximately 0.115 µM. Such inhibiting effect of rolipram was mediated by activating cAMP signaling because the cAMP analog dibutyryl-cAMP produced the same inhibitory effect in Raw264.7 cells. In addition, the Epac inhibitor ESI-09 did not reverse the inhibitory effect of rolipram, while the PKA inhibitor Rp-8-CPT-cAMP reversed the inhibition by approximately 57 %, suggesting that the inhibitory effect of rolipram on the IFN-β expression was mediated by activation of the cAMP/PKA, but not cAMP/Epac signal pathway. Moreover, the PKA activator 6-Bnz-cAMP significantly decreased the LPS-induced IFN-β expression at the level similar to that of rolipram. Using the peritoneal macrophages isolated from PDE4 null mice and the corresponding wild-type mice, we further found that the LPS-induced IFN-β expression in PDE4B-/- macrophages, but not PDE4A-/- or PDE4D-/- macrophages, was significantly decreased, and the level of expression was similar to that of PDE4B+/+ macrophages treated with rolipram. Additionally, rolipram did not further decrease the IFN- expression in PDE4B-/- macrophages. Contrarily, PDE4A-/- and PDE4D-/- macrophages, like their wild-type macrophages, exhibited significant reduction in IFN-β expression in the presence of rolipram. These results demonstrated that the rolipram effect on the IFN-β expression was mediated by inhibition of PDE4B. To explore whether inhibition of IFN-β expression by rolipram acts through regulation of TRIF-dependent signal pathway, the activation of the transcription factor IRF3 and its upstream factor TBK1 was monitored by western blotting. The results showed that LPS-induced IRF3 phosphorylation in Raw264.7 cells was elevated with time until 3 h, but was not altered by rolipram until 5 h after LPS stimulation. LPS-induced TBK1 phosphorylation was unchanged by rolipram up to 5 h of LPS stimulateion. Collectively, our data demonstrated that inhibition of PDE4B is sufficient to block LPS-induced IFN-β expression via activation of cAMP/PKA signal pathway in mouse macrophages but not by regulation of TLR4/TRIF/TBK1/IRF3 signal pathway.
關鍵字(中) ★ 環狀核苷酸磷酸二酯酶4
★ 巨噬細胞
★ 干擾素-β
★ 環狀核苷酸
關鍵字(英) ★ Phosphodiesterase4
★ Macrophage
★ IFN-β
★ cAMP
論文目次 中文摘要 i
英文摘要 iii
誌謝 v
目錄 vi
圖目錄 ix
縮寫檢索表 x
第一章 緒論 1
1-1 環狀核苷酸磷酸二酯酶( cyclic nucleotide phosphodiesterase;PDE ) 1
1-2 PDE4家族 2
1-3 cAMP訊息傳遞路徑 4
1-4 cAMP與免疫反應 5
1-5 Toll-like receptor 3 (TLR3)與TLR4的訊息傳導 6
1-6 干擾素-(Interferon-;IFN-) 9
1-7 cAMP與IFN-基因表現 11
第二章 研究動機與目的 12
第三章 實驗材料與方法 13
3-1 實驗材料 13
3-1-1 實驗用細胞株 13
3-1-2 實驗用小鼠 13
3-1-3 實驗用藥品 13
3-1-3-1 細胞操作相關溶液 13
3-1-3-2 化學藥品 14
3-1-3-3 小分子藥劑 15
3-1-3-4 抗體 15
3-2 實驗方法 16
3-2-1 巨噬細胞之培養與處理方法 16
3-2-1-1 Raw264.7巨噬細胞的培養 16
3-2-1-2 Raw264.7巨噬細胞的藥物處理 16
3-2-2 小鼠腹腔巨噬細胞( Mouse peritoneal macrophage )的培養 16
3-2-2-1 B cell panning培養皿的製備 16
3-2-2-2 小鼠腹腔巨噬細胞的收取 17
3-2-2-3 小鼠腹腔巨噬細胞的藥物處理 17
3-2-3 即時聚合酶連鎖反應(Real-time polymerase chain reaction;Real-time PCR;qPCR) 18
3-2-3-1 萃取巨噬細胞的RNA 18
3-2-3-2 反轉錄製作cDNA 18
3-2-3-3 cDNA cleaning 19
3-2-3-4 即時聚合酶連鎖反應(Real-time PCR) 19
3-2-4 西方點墨法(Western blot) 20
3-2-4-1 蛋白質萃取 20
3-2-4-2 蛋白質濃度檢測 20
3-2-4-3 西方點墨法 20
第四章 實驗結果 23
4-1 PDE4抑制劑對LPS誘導Raw264.7巨噬細胞表現IFN-的影響 23
4-2 Rolipram抑制IFN-表現的cAMP訊息傳導路徑 23
4-3 在巨噬細胞中PDE4B參與LPS刺激IFN-表現的調控 24
4-4 抑制PDE4對TLR4訊息傳導分子IRF3與TBK1的影響 25
第五章 討論 27
參考文獻 31
第六章 圖與圖解 39
附圖 49
參考文獻 Adhikari, A., et al. (2007). "Ubiquitin-mediated activation of TAK1 and IKK." Oncogene 26(22): 3214-3226.
Aggarwal, B. B. (2003). "Signalling pathways of the TNF superfamily: A double-edged sword." Nature Reviews Immunology 3(9): 745-756.
Akira, S., et al. (2006). "Pathogen recognition and innate immunity." Cell 124(4): 783-801.
Akashi-Takamura, S. and K. Miyake (2008). "TLR accessory molecules." Current Opinion in Immunology 20(4): 420-425.
Aronoff, D. M., et al. (2006). "Differences between macrophages and dendritic cells in the cyclic AMP-dependent regulation of lipopolysaccharide-induced cytokine and chemokine synthesis." Journal of Interferon and Cytokine Research 26(11): 827-833.
Bhoj, V. G., et al. (2008). "MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus." Proceedings of the National Academy of Sciences of the United States of America 105(37): 14046-14051.
Blasius, A. L. and B. Beutler (2010). "Intracellular Toll-like Receptors." Immunity 32(3): 305-315.
Bos, J. L., et al. (2001). "Rap1 signalling: Adhering to new models." Nature Reviews Molecular Cell Biology 2(5): 369-377.
Bos, J. L., et al. (2003). "The role of Rap1 in integrin-mediated cell adhesion." Biochemical Society Transactions 31: 83-86.
Bos, J. L. (2005). "Linking Rap to cell adhesion." Current Opinion in Cell Biology 17(2): 123-128.
Brian K. Kobilka. (2007). “G Protein Coupled Receptor Structure and Activation.” Biochim Biophys Acta 1768(4): 794–807.
Chen, N. J., et al. (2008). "Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors." Proceedings of the National Academy of Sciences of the United States of America 105(34): 12429-12434.
Chung, K. F. (2006). "Phosphodiesterase inhibitors in airways disease." European Journal of Pharmacology 533(1-3): 110-117.
Collado-Hidalgo, A., et al. (2006). "Adrenergic inhibition of innate anti-viral response: PKA blockade of Type I interferon gene transcription mediates catecholamine support for HIV-1 replication." Brain Behavior and Immunity 20(6): 552-563.
Conti, M. and Beavo, J (2007). "Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling." Annu Rev Biochem 76: 481-511.
Degraaf, A. J., et al. (2014). “Prostaglandin E2 reduces Toll-like Receptor 4 Expression in Alveolar Macrophages by Inhibition of Translation.” Am J Respir Cell Mol Biol 51(2):242-50
D′Sa C., et al. (2002). “Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice variants by cAMP signaling in primary cortical neurons.” J Neurochem 81(4):745-57.
Fan Chung K. (2006). “Phosphodiesterase inhibitors in airways disease.” Eur J Pharmacol 533(1-3):110-7.
Fine, J. S., et al. (2001). "Evaluation of signal transduction pathways in chemoattractant-induced human monocyte chemotaxis." Inflammation 25(2): 61-67.
Fitzgerald, K. A. (2011). "The Interferon Inducible Gene: Viperin." Journal of Interferon and Cytokine Research 31(1): 131-135.
Hamilton, M. J., et al. (2010). "TLR Agonists That Induce IFN-beta Abrogate Resident Macrophage Suppression of T Cells." Journal of Immunology 185(8): 4545-4553.
Harvath, L., et al. (1991). "Camp and Human Neutrophil Chemotaxis - Elevation of Camp Differentially Affects Chemotactic Responsiveness." Journal of Immunology 146(1): 224-232.
Hemmi, H., et al. (2004). "The roles of two I kappa B kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection." Journal of Experimental Medicine 199(12): 1641-1650.
Holz, G. G., et al. (2006). "Cell physiology of cAMP sensor Epac." Journal of Physiology-London 577(1): 5-15.
Honda, K. and T. Taniguchi (2006). "IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors." Nature Reviews Immunology 6(9): 644-658.
Houslay MD and Adams DR. (2003). “PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization.” Biochem J; 370(Pt 1):1-18.
Houslay MD and Baillie GS. (2003). “The role of ERK2 docking and phosphorylation of PDE4 cAMP phosphodiesterase isoforms in mediating cross-talk between the cAMP and ERK signalling pathways.” Biochem Soc Trans (Pt 6):1186-90.
Houslay, M. D., et al. (2005). "Phosphodiesterase-4 as a therapeutic target." Drug Discovery Today 10(22): 1503-1519.
Häcker, H., et al. (2011). "Expanding TRAF function: TRAF3 as a tri-faced immune regulator." Nature Reviews Immunology 11(7): 457-468.
Ikeda, F., et al. (2007). "Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes." Embo Journal 26(14): 3451-3462.
Jiang, Z. F., et al. (2004). "Toll-like receptor 3-mediated activation of NF-kappa B and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing INF-beta." Proceedings of the National Academy of Sciences of the United States of America 101(10): 3533-3538.
Jin, S. L. C. and Conti, M. (2012). “Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses.” Proc Natl Acad Sci U S A 99(11):7628-33.
Jin, S. L. C., et al. (2005). "Specific role of phosphodiesterase 4B in lipopolysaccharide-induced signaling in mouse macrophages." Journal of Immunology 175(3): 1523-1531.
Jin, S. L. C., et al. (2007). “Insights into the Phisiological Function of PDE4 from Knockout Mice.” Cyclic Nucleotide Phosphodiesterases in Health and Disease Chapter 16 323-339
Jin, S. L. C., et al. (2010). "Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma." Journal of Allergy and Clinical Immunology 126(6): 1252-U1283.
Jin, S. L. C., et al. (2012). “Phosphodiesterase 4 and its inhibitors in inflammatory diseases. “ Chang Gung Med J 35(3):197-210.
Kang, G. X., et al. (2006). "cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells." Journal of Physiology-London 573(3): 595-609.
Kaupp, U. B. and R. Seifert (2002). "Cyclic nucleotide-gated ion channels." Physiological Reviews 82(3): 769-824.
Kawai, T. and Akira, S (2010). "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors." Nature Immunology 11(5): 373-384.
Kinbara, K., et al. (2003). "Ras GTPases: Integrins′ friends or foes?" Nature Reviews Molecular Cell Biology 4(10): 767-776.
Kobilka, B. K. (2007). "G protein coupled receptor structure and activation." Biochimica Et Biophysica Acta-Biomembranes 1768(4): 794-807.
Kooistra, M. R. H., et al. (2007). "Rap1: a key regulator in cell-cell junction formation." Journal of Cell Science 120(1): 17-22.
Kopperud, R., et al. (2003). "cAMP effector mechanisms. Novel twists for an ′old′ signaling system." Febs Letters 546(1): 121-126.
Koopman WJ, et al. (2003). “R-Ras alters Ca2+ homeostasis by increasing the Ca2+ leak across the endoplasmic reticular membrane.” J Biol Chem 278(16):13672-9.
Kraan, T. C. T. M. V., et al. (1995). "Prostaglandin-E2 Is a Potent Inhibitor of Human Interleukin-12 Production." Journal of Experimental Medicine 181(2): 775-779.
Laguette, N. and M. Benkirane (2012). "How Samhd1 changes our view of viral restriction." Trends in Immunology 33(1): 26-33.
Leemhuis, J., et al. (2002). "The protein kinase A inhibitor H89 acts on cell morphology by inhibiting rho kinase." Journal of Pharmacology and Experimental Therapeutics 300(3): 1000-1007.
Lester, S. N. and K. Li (2014). "Toll-Like Receptors in Antiviral Innate Immunity." Journal of Molecular Biology 426(6): 1246-1264.
Lignitto, L., et al. (2011) “Control of PKA stability and signalling by the RING ligase praja2” Nat Cell Biol 13(4): 412-22.
Liu, S. Y., et al. (2013). "Interferon-Inducible Cholesterol-25-Hydroxylase Broadly Inhibits Viral Entry by Production of 25-Hydroxycholesterol." Immunity 38(1): 92-105.
Li, X. D., et al. (2013). "Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects." Science 341(6152): 1390-1394.
Malim, M. H. and P. D. Bieniasz (2012). "HIV Restriction Factors and Mechanisms of Evasion." Cold Spring Harbor Perspectives in Medicine 2(5).
Mehats, C., et al. (2002)“Cyclic nucleotide phosphodiesterases and their role in endocrine cell signaling.” Trends Endocrinol Metab 13(1):29-35.
Omori, K. and J. Kotera (2007). "Overview of PDEs and their regulation." Circulation Research 100(3): 309-327.
Page, C.P. and Spina, D. (2011). “Phosphodiesterase inhibitors in the treatment of inflammatory diseases.” Handb Exp Pharmacol (204):391-414.
Park, S. J., et al. (2012). "Resveratrol Ameliorates Aging-Related Metabolic Phenotypes by Inhibiting cAMP Phosphodiesterases." Cell 148(3): 421-433.
Peter, D., et al. (2007). "Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4(+) T cells: Predominant role of PDE4D." Journal of Immunology 178(8): 4820-4831.
Perry, A. K., et al. (2004). "Differential requirement for TANK-binding kinase-1 in type I interferon responses to toll-like receptor activation and viral infection." Journal of Experimental Medicine 199(12): 1651-1658.
Ping Wu and Peng Wang (2004). “Per-Arnt-Sim domain-dependent association of cAMP-phosphodiesterase 8A1 with IκB proteins.” PNAS 0407649101
Press, N.J. and Banner, K.H. (2009). “PDE4 inhibitors - a review of the current field.” Prog Med Chem 47:37-74.
Roscioni, S. S., et al. (2008). "Epac: effectors and biological functions." Naunyn-Schmiedebergs Archives of Pharmacology 377(4-6): 345-357.
Roya Zoraghi, et al. (2003). “Properties and Functions of GAF Domains in Cyclic Nucleotide Phosphodiesterases and Other Proteins.” Mol Pharmacol 65:267–278.
Sancho-Shimizu, V., et al. (2011). "Inborn errors of anti-viral interferon immunity in humans." Current Opinion in Virology 1(6): 487-496.
Sara S, et al. (2008). "Epac: effectors and biological functions" Naunyn-Schmiedeberg′s Arch Pharmacol 377: 345-357
Sato, M., et al. (1998). "Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7." Febs Letters 441(1): 106-110.
Sato, M., et al. (2000). "Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction." Immunity 13(4): 539-548.
Sato, M., et al. (2001). "The interferon system and interferon regulatory factor transcription factors - studies from gene knockout mice." Cytokine & Growth Factor Reviews 12(2-3): 133-142.
Schoggins, J. W. (2014). "Interferon-stimulated genes: roles in viral pathogenesis." Current Opinion in Virology 6: 40-46.
Schoggins, J. W., et al. (2014). "Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity." Nature 505(7485): 691-+.
Seo, J. Y., et al. (2011). "Viperin: A Multifunctional, Interferon-Inducible Protein that Regulates Virus Replication." Cell Host & Microbe 10(6): 534-539.
Sette, C. and M. Conti (1996). "Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase - Involvement of serine 54 in the enzyme activation." Journal of Biological Chemistry 271(28): 16526-16534.
Self, A. J., et al. (2001). "Analysis of R-Ras signalling pathways." Journal of Cell Science 114(7): 1357-1366.
Serezani, C. H., et al. (2008). "Cyclic AMP - Master regulator of innate immune cell function." American Journal of Respiratory Cell and Molecular Biology 39(2): 127-132.
Stork, P. J. S. and J. M. Schmitt (2002). "Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation." Trends in Cell Biology 12(6): 258-266.
Swinnen, J.V., et al. (1989) “Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes.” Proc Natl Acad Sci U S A 86(14):5325-9.
Takeda, K., et al. (2003). "Toll-like receptors." Annual Review of Immunology 21: 335-376.
Takeuchi, O. and S. Akira (2008). "MDA5/RIG-I and virus recognition." Current Opinion in Immunology 20(1): 17-22.
Taro Kawai and Shizuo Akira. (2010) “The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.” Nature Immunology 11: 373–384
Todd, S. and S. L. Naylor (1992). "New Chromosomal Mapping Assignments for Argininosuccinate Synthetase Pseudogene-1, Interferon-Beta-3 Gene, and the Diazepam Binding Inhibitor Gene." Somatic Cell and Molecular Genetics 18(4): 381-385.
Torphy, T. J. (1998). "Phosphodiesterase isozymes - Molecular targets for novel antiasthma agents." American Journal of Respiratory and Critical Care Medicine 157(2): 351-370.
U Benjamin Kaupp and Reinhard Seifert. (2002). “Cyclic nucleotide-gated ion channels.” Physiol Rev 82(3):769-824.
Vicini, E. and Conti, M. (1997). “Characterization of an intronic promoter of a cyclic adenosine 3′,5′-monophosphate (cAMP)-specific phosphodiesterase gene that confers hormone and cAMP inducibility.” Mol Endocrinol 11(7):839-50.
Wang, T., et al. (2004). "Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis." Nature Medicine 10(12): 1366-1373.
Wu, P. and P. Wang (2004). "Per-Arnt-Sim domain-dependent association of cAMP-phosphodiesterase 8A1 with I kappa B proteins." Proceedings of the National Academy of Sciences of the United States of America 101(51): 17634-17639.
Xu, X. J., et al. (2008). "Prostaglandin E(2) suppresses lipopolysaccharide-stimulated IFN-beta production." Journal of Immunology 180(4): 2125-2131.
Youn, H. S., et al. (2005). "Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: Molecular targets are TBK1 and RIP1 in TRIF complex." Journal of Immunology 175(5): 3339-3346.
Zoraghi, R., et al. (2004). "Properties and functions of GAF domains in cyclic nucleotide phosphodiesterases and other proteins." Molecular Pharmacology 65(2): 267-278.
指導教授 金秀蓮(S.-L. Catherine Jin) 審核日期 2014-8-28
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