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姓名	賴秋蓉(Ciou-rong Lai)  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與cAMP訊息傳導在小鼠巨噬細胞中對於CCL3生成之調控 (Regulation of CCL3 production by phosphodiesterase 4 and cAMP signaling in mouse macrophages)
相關論文	★ PDE抑制劑與cAMP訊號傳導對類風濕性關節炎小鼠模型中CD4+ T細胞釋放IFN-g與IL-17A之調控 ★ PDE4和cAMP訊號傳導於小鼠骨髓細胞分化為樹突細胞之角色 ★ 利用斑馬魚研究肝臟疾病和肝癌之發生：B型肝炎病毒X抗原，黃麴毒素，p53突變，src和edn1的致癌作用及其協同效應 ★ 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 ★ 抑制環狀核苷酸磷酸二酯酶 3 (PDE3)對 3T3-L1 脂肪細胞內蛋白質表現之影響 ★ 環狀核苷酸磷酸二酯酶4B對小鼠樹突細胞分化與CXCR4表現之調控 ★ 利用聚乙烯亞胺輸送環狀核苷酸磷酸二酯酶4B之專一性反義寡核苷酸可抑制LPS刺激小鼠巨噬細胞釋放TNF-α ★ PDE4與PDE3抑制劑對膠原蛋白誘發DBA/1小鼠關節炎及釋放發炎激素IFN-γ與IL-17A的協同調控作用 ★ 環狀核苷酸磷酸二酯酶4B對內毒素誘導巨噬細胞 產生IL-1Ra和樹突細胞表現TLRs之影響 及其對乾癬症生成之潛在角色 ★ 環狀核苷酸磷酸二脂酶4B對內毒素刺激小鼠樹突細胞表現NOD1與CXCR4的影響 ★ TDAG8 participates in different phases of neuropathic pain by regulating distinct pathways of substance P ★ Innovative Mind-Body Intervention Day Easy Exercise Increases Peripheral Blood CD34+ Cells and Attenuates Back Pain in Adults ★ Viscolin對不同免疫細胞發炎反應的影響 ★ 環狀腺苷單磷酸與其它訊息傳遞因子對脂肪細胞釋放阻抗素之影響 ★ 環狀核苷酸磷酸二酯酶4B對於小鼠T細胞功能之調節 ★ 巨噬細胞中抑制PDE4對LPS誘導發炎反應之調控
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摘要(中)	CCL3又稱為MIP-1α，是CC趨化激素家族的一員。它可由巨噬細胞、淋巴細胞、嗜中性白血球與樹突細胞生成及釋放，並藉由其趨化與促發炎特性來調控發炎反應。然而，目前對CCL3生成與作用的調控機制尚不甚明瞭。文獻報導已顯示，在巨噬細胞內增加cAMP濃度可抑制LPS對CCL3的釋放。已知PDE4在許多發炎細胞中藉著水解cAMP來調控cAMP的濃度，而抑制PDE4活性有減緩發炎反應的功效。因此本研究的主要目的是探討PDE4是否藉由影響cAMP的訊息傳導路徑來參與調控CCL3的生成。實驗結果顯示，LPS處理RAW 264.7與小鼠腹腔巨噬細胞可刺激CCL3的釋放，且隨著時間與LPS濃度增加而上升。PDE4抑制劑rolipram則可有效地抑制此LPS刺激所產生之CCL3 mRNA的表現與蛋白質的釋放，其IC50約為0.1 μM。再者，單獨處理dibutyryl-cAMP或PKA活化劑6-Bnz-cAMP也會抑制CCL3的釋放，而Epac活化劑8-pCPT-2’-O-Me-cAMP則無影響，同時，PKA抑制劑Rp-8-CPT-cAMPS會部分回復rolipram對CCL3的抑制作用。由此我們推論， PDE4抑制劑對CCL3釋放的抑制是藉由增加cAMP進而活化PKA所致。本研究以LPS刺激PDE4基因剔除巨噬細胞，進一步證實，剔除PDE4B而非PDE4A或PDE4D可顯著降低CCL3的釋放，而此下降程度與野生型巨噬細胞處理rolipram時的抑制作用相當。此結果證明rolipram對CCL3的抑制是由於抑制了PDE4B的活性所致。此外，CCL3對小鼠脾臟T細胞的趨化作用也會被rolipram所抑制。綜合本研究的結果證明，在巨噬細胞內PDE4B可調控cAMP的訊息傳導進而影響LPS/TLR4/CCL3的免疫反應。
摘要(英)	CCL3, also known as macrophage inflammatory protein 1 alpha (MIP-1α), is a member of the C-C chemokine family. It is produced by macrophages, lymphocytes, neutrophils, and dendritic cells, and exerts chemotactic and proinflammatory effects. The mechanism underlying its production and action, however, is largely unknown. It has been shown that increasing intracellular cAMP concentration in macrophage suppresses the LPS-induced CCL3 secretion. Type 4 cAMP-specific phosphodisterases (PDE4s) are known to regulate cAMP levels in most inflammatory cells by hydrolyzing cAMP and, thereby inhibition of PDE4 activity can increase cAMP concentrations in these cells. In this study, we aimed to determine whether PDE4 is involved in regulation of the CCL3 production via activation of cAMP signal pathways. By stimulation of Raw264.7 and mouse peritoneal macrophages with LPS, we found that the CCL3 release was increased in a time- and dose-dependent manner within 8 h. The PDE4 inhibitor rolipram effectively suppressed the CCL3 mRNA expression and protein release with the IC50 of approximately 0.1 μM. Moreover, the LPS-induced CCL3 release was also dose-dependently inhibited by the PKA activator 6-Bnz-cAMP, but not by the Epac activator 8-pCPT-2’-O-Me-cAMP, suggesting that the effect of PDE4 inhibition on the CCL3 release was caused by increasing cAMP and activation of PKA. In addition, the attenuated CCL3 release caused by rolipram was partially reversed by the PKA inhibitor Rp-8-CPT-cAMPS. Using PDE4-deficient macrophages, we further found that LPS-stimulated PDE4B-/-, but not PDE4A-/- or PDE4D-/-, macrophages produced a significant decrease in the CCL3 release, and this reduction was similar to that observed in the wild-type macrophages inhibition by rolipram. This demonstrated that the inhibitory effect of rolipram on the CCL3 release was mediated by the inhibitor of the PDE4B isoform. Moreover, the chemotaxis of the splenic T cells induced by CCL3 was also inhibited by rolipram. Taken together, these findings demonstrated that PDE4B and the cAMP/PKA signaling play an essential role in the LPS/TLR4/CCL3 signal pathway in macrophages.
關鍵字(中)	★ CC趨化激素配體3 ★ 環磷酸腺苷 ★ 環狀核苷酸磷酸二酯酶4 ★ 巨噬細胞 ★ T細胞 ★ 趨化作用	關鍵字(英)	★ CCL3 ★ cAMP ★ PDE4 ★ Macrophage ★ T cell ★ Chemotaxis
論文目次	目錄 中文摘要 i 英文摘要 ii 誌謝 iv 目錄 v 圖目錄 viii 縮寫檢索表 ix 一 緒論 1 1-1 Chemokine 1 1-2 Chemokine與Chemokine receptor 2 1-3 Macrophage inflammatory protein-1α（MIP-1α/CCL3） 2 1-4 CCL3與免疫反應 3 1-5 Adenosine 3’,5’-cyclic monophosphate（cAMP）訊息傳導路徑 4 1-6 cAMP的免疫調節作用 5 1-7 環狀核苷酸磷酸二脂酶（Cyclic nucleotide phosphodiesterase；PDE） 6 1-8 PDE4 7 1-9 PDE4與免疫調節反應 8 二 實驗目的 10 三 材料與方法 11 3-1 材料 11 3-1-1 細胞培養 11 3-1-2 藥品試劑 11 3-1-3 實驗動物 12 3-1-4 實驗細胞株 12 3-2 方法 13 3-2-1 巨噬細胞株之培養及處理方法 13 3-2-1-1 巨噬細胞株之培養 13 3-2-1-2 巨噬細胞株之藥劑處理 13 3-2-2 小鼠巨噬細胞之收取、培養及處理 13 3-2-2-1 配置B cell panning培養皿 13 3-2-2-2 小鼠腹腔巨噬細胞之收取、純化與培養 14 3-2-2-3 小鼠腹腔巨噬細胞之藥物處理 14 3-2-3 酵素免疫分析法(Enzyme-Linked Immunosorbent Assay, ELISA) 14 3-2-4 萃取細胞RNA 15 3-2-5 即時聚合酶連鎖反應(Real-time Polymerase Chain Reaction, Real-time PCR) 16 1. 反轉錄反應(Reverse Transcription) 16 2. 即時聚合酶連鎖反應 16 3-2-6 小鼠脾臟T細胞之收取、培養 17 3-2-7 細胞趨化反應分析(Chemotaxis assay) 17 四 實驗結果 19 4-1 PDE4抑制劑與cAMP對LPS刺激巨噬細胞釋放CCL3之影響 19 4-2 PDE4抑制劑對LPS刺激巨噬細胞表現CCL3基因之影響 20 4-3 活化PKA與Epac對LPS刺激巨噬細胞釋放CCL3之影響 20 4-4 抑制PKA對LPS刺激巨噬細胞釋放CCL3之影響 21 4-5 剔除PDE4B基因可降低LPS對巨噬細胞釋放CCL3的作用 22 4-6 Rolipram抑制CCL3誘導小鼠脾臟T細胞之趨化反應 22 五 討論 24 5-1 LPS誘導CCL3釋放之訊息傳導路徑 24 5-2 PDE4B對LPS刺激巨噬細胞釋放CCL3之調控 25 5-3 PDE4與cAMP訊息傳導對LPS誘導CCL3釋放之影響 27 5-4 Rolipram對T細胞進行趨化作用之影響 28 六 圖與圖解 29 參考文獻 40 附圖 51 圖目錄 圖一 LPS刺激巨噬細胞釋放CCL3 29 圖二 抑制PDE4對LPS刺激巨噬細胞釋放CCL3之影響 30 圖三 Dibutyryl-cAMP（db-cAMP）對LPS刺激巨噬細胞釋放CCL3之影響 31 圖四 抑制PDE4對LPS刺激巨噬細胞產生CCL3 mRNA之影響 32 圖五 活化PKA對LPS刺激巨噬細胞釋放CCL3之影響 33 圖六 活化EPAC對LPS刺激巨噬細胞釋放CCL3之影響 34 圖七 抑制PKA對LPS刺激巨噬細胞釋放CCL3之影響 35 圖八 剔除PDE4A、PDE4B或PDE4D對LPS刺激CCL3釋放之影響 36 圖九 CCL3誘導小鼠脾臟T細胞產生趨化反應之影響 38 圖十 Rolipram對CCL3誘導小鼠脾臟T細胞產生趨化運動之影響 39
參考文獻	參考文獻 Ariga, M., B. Neitzert, et al. (2004). "Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammation." J Immunol 173(12): 7531-7538. Aronoff, D. M., C. Canetti, et al. (2004). "Prostaglandin E2 inhibits alveolar macrophage phagocytosis through an E-prostanoid 2 receptor-mediated increase in intracellular cyclic AMP." J Immunol 173(1): 559-565. Aronoff, D. M., J. K. Carstens, et al. (2006). "Short communication: differences between macrophages and dendritic cells in the cyclic AMP-dependent regulation of lipopolysaccharide-induced cytokine and chemokine synthesis." J Interferon Cytokine Res 26(11): 827-833. Bacon, K., M. Baggiolini, et al. (2002). "Chemokine/chemokine receptor nomenclature." J Interferon Cytokine Res 22(10): 1067-1068. Balashov, K. E., J. B. Rottman, et al. (1999). "CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions." Proc Natl Acad Sci U S A 96(12): 6873-6878. Barnes, P. J. (2008). "The cytokine network in asthma and chronic obstructive pulmonary disease." J Clin Invest 118(11): 3546-3556. Beard, M. B., A. E. Olsen, et al. (2000). "UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions." J Biol Chem 275(14): 10349-10358. Beavo, J. A. (1995). "Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms." Physiol Rev 75(4): 725-748. Bender, A. T. and J. A. Beavo (2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use." Pharmacol Rev 58(3): 488-520. Biswas, S. K., L. Gangi, et al. (2006). "A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation)." Blood 107(5): 2112-2122. Bonecchi, R., G. Bianchi, et al. (1998). "Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s." J Exp Med 187(1): 129-134. Bonecchi, R., E. Galliera, et al. (2009). "Chemokines and chemokine receptors: an overview." Front Biosci 14: 540-551. Bos, J. L. (2003). "Epac: a new cAMP target and new avenues in cAMP research." Nat Rev Mol Cell Biol 4(9): 733-738. Bryn, T., M. Mahic, et al. (2006). "The cyclic AMP-Epac1-Rap1 pathway is dissociated from regulation of effector functions in monocytes but acquires immunoregulatory function in mature macrophages." J Immunol 176(12): 7361-7370. Buenestado, A., S. Grassin-Delyle, et al. (2012). "Roflumilast inhibits the release of chemokines and TNF-alpha from human lung macrophages stimulated with lipopolysaccharide." Br J Pharmacol 165(6): 1877-1890. Canetti, C., C. H. Serezani, et al. (2007). "Activation of phosphatase and tensin homolog on chromosome 10 mediates the inhibition of FcgammaR phagocytosis by prostaglandin E2 in alveolar macrophages." J Immunol 179(12): 8350-8356. Castro, A., M. J. Jerez, et al. (2005). "Cyclic nucleotide phosphodiesterases and their role in immunomodulatory responses: advances in the development of specific phosphodiesterase inhibitors." Med Res Rev 25(2): 229-244. Charo, I. F. and R. M. Ransohoff (2006). "The many roles of chemokines and chemokine receptors in inflammation." N Engl J Med 354(6): 610-621. Cheng, X., Z. Ji, et al. (2008). "Epac and PKA: a tale of two intracellular cAMP receptors." Acta Biochim Biophys Sin (Shanghai) 40(7): 651-662. Chui, R. and K. Dorovini-Zis (2010). "Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide." J Neuroinflammation 7: 1. Conti, M. and J. Beavo (2007). "Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling." Annu Rev Biochem 76: 481-511. Conti, M., G. Nemoz, et al. (1995). "Recent progress in understanding the hormonal regulation of phosphodiesterases." Endocr Rev 16(3): 370-389. D’Sa, C., A. J. Eisch, et al. (2005). "Differential expression and regulation of the cAMP-selective phosphodiesterase type 4A splice variants in rat brain by chronic antidepressant administration." Eur J Neurosci 22(6): 1463-1475. David, M., E. Petricoin, 3rd, et al. (1996). "Activation of protein kinase A inhibits interferon induction of the Jak/Stat pathway in U266 cells." J Biol Chem 271(9): 4585-4588. Dey, R., N. Majumder, et al. (2007). "Induction of host protective Th1 immune response by chemokines in Leishmania donovani-infected BALB/c mice." Scand J Immunol 66(6): 671-683. Engels, P., M. Sullivan, et al. (1995). "Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C)." FEBS Lett 358(3): 305-310. Essayan, D. M. (2001). "Cyclic nucleotide phosphodiesterases." J Allergy Clin Immunol 108(5): 671-680. Fahey, T. J., 3rd, K. J. Tracey, et al. (1992). "Macrophage inflammatory protein 1 modulates macrophage function." J Immunol 148(9): 2764-2769. Fan Chung, K. (2006). "Phosphodiesterase inhibitors in airways disease." Eur J Pharmacol 533(1-3): 110-117. Grandoch, M., V. Bujok, et al. (2009). "Epac inhibits apoptosis of human leukocytes." J Leukoc Biol 86(4): 847-849. Grant, V., A. E. King, et al. (2005). "PGE/cAMP and GM-CSF synergise to induce a pro-tolerance cytokine profile in monocytic cell lines." Biochem Biophys Res Commun 331(1): 187-193. Grove, M. and M. Plumb (1993). "C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene." Mol Cell Biol 13(9): 5276-5289. Hansen, G., S. Jin, et al. (2000). "Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D." Proc Natl Acad Sci U S A 97(12): 6751-6756. Hatzelmann, A. and C. Schudt (2001). "Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro." J Pharmacol Exp Ther 297(1): 267-279. Hertz, A. L., A. T. Bender, et al. (2009). "Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages." Proc Natl Acad Sci U S A 106(51): 21978-21983. Holgate, S. T., K. S. Bodey, et al. (1997). "Release of RANTES, MIP-1 alpha, and MCP-1 into asthmatic airways following endobronchial allergen challenge." Am J Respir Crit Care Med 156(5): 1377-1383. Horuk, R. (2007). "Chemokines." ScientificWorldJournal 7: 224-232. Houslay, M. D. (2001). "PDE4 cAMP-specific phosphodiesterases." Prog Nucleic Acid Res Mol Biol 69: 249-315. Houslay, M. D. and D. R. Adams (2003). "PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization." Biochem J 370(Pt 1): 1-18. Houslay, M. D., P. Schafer, et al. (2005). "Keynote review: phosphodiesterase-4 as a therapeutic target." Drug Discov Today 10(22): 1503-1519. Jin, S. L. and M. Conti (2002). "Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses." Proc Natl Acad Sci U S A 99(11): 7628-7633. Jin, S. L., S. L. Ding, et al. (2012). "Phosphodiesterase 4 and its inhibitors in inflammatory diseases." Chang Gung Med J 35(3): 197-210. Jin, S. L., S. Goya, et al. (2010). "Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma." J Allergy Clin Immunol 126(6): 1252-1259 e1212. Jin, S. L., L. Lan, et al. (2005). "Specific role of phosphodiesterase 4B in lipopolysaccharide-induced signaling in mouse macrophages." J Immunol 175(3): 1523-1531. Jin, S. L., F. J. Richard, et al. (1999). "Impaired growth and fertility of cAMP-specific phosphodiesterase PDE4D-deficient mice." Proc Natl Acad Sci U S A 96(21): 11998-12003. Jin, S. L., W. Richter, et al. (2007). "Insights into the Physiological Functions of PDE4 from Knockout Mice." Cyclic Nucleotide Phosphodiesterases in Health and Disease Chapter 16 323-339 Jing, H., J. H. Yen, et al. (2004). "A novel signaling pathway mediates the inhibition of CCL3/4 expression by prostaglandin E2." J Biol Chem 279(53): 55176-55186. Kaneko, T., R. Alvarez, et al. (1995). "Elevated intracellular cyclic AMP inhibits chemotaxis in human eosinophils." Cell Signal 7(5): 527-534. Kawashita, E., D. Tsuji, et al. (2011). "Prostaglandin E2 reverses aberrant production of an inflammatory chemokine by microglia from Sandhoff disease model mice through the cAMP-PKA pathway." PLoS One 6(1): e16269. Kopperud, R., A. E. Christensen, et al. (2002). "Formation of inactive cAMP-saturated holoenzyme of cAMP-dependent protein kinase under physiological conditions." J Biol Chem 277(16): 13443-13448. Kuklina, E. M. and S. V. Shirshev (2000). "Role of cAMP-dependent signal transduction in the control of T lymphocyte activation." Biochemistry (Mosc) 65(6): 629-639. Kwak, H. J., J. S. Song, et al. (2005). "Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation." J Pharmacol Exp Ther 315(3): 1188-1195. Lahrtz, F., L. Piali, et al. (1998). "Chemokines and chemotaxis of leukocytes in infectious meningitis." J Neuroimmunol 85(1): 33-43. Larrubia, J. R., S. Benito-Martinez, et al. (2008). "Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection." World J Gastroenterol 14(47): 7149-7159. Lehnart, S. E., X. H. Wehrens, et al. (2005). "Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias." Cell 123(1): 25-35. Lorenowicz, M. J., J. van Gils, et al. (2006). "Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis." J Leukoc Biol 80(6): 1542-1552. Luster, A. D. (1998). "Chemokines--chemotactic cytokines that mediate inflammation." N Engl J Med 338(7): 436-445. Maurer, M. and E. von Stebut (2004). "Macrophage inflammatory protein-1." Int J Biochem Cell Biol 36(10): 1882-1886. Maurice, D. H. (2011). "Subcellular signaling in the endothelium: cyclic nucleotides take their place." Curr Opin Pharmacol 11(6): 656-664. Menten, P., A. Wuyts, et al. (2002). "Macrophage inflammatory protein-1." Cytokine Growth Factor Rev 13(6): 455-481. Michalski, J. M., G. Golden, et al. (2012). "PDE4: a novel target in the treatment of chronic obstructive pulmonary disease." Clin Pharmacol Ther 91(1): 134-142. Mitin, N., K. L. Rossman, et al. (2005). "Signaling interplay in Ras superfamily function." Curr Biol 15(14): R563-574. Miyazaki, D., T. Nakamura, et al. (2005). "Macrophage inflammatory protein-1alpha as a costimulatory signal for mast cell-mediated immediate hypersensitivity reactions." J Clin Invest 115(2): 434-442. Monfar, M., K. P. Lemon, et al. (1995). "Activation of pp70/85 S6 kinases in interleukin-2-responsive lymphoid cells is mediated by phosphatidylinositol 3-kinase and inhibited by cyclic AMP." Mol Cell Biol 15(1): 326-337. Mortaz, E., A. D. Kraneveld, et al. (2009). "Effect of cigarette smoke extract on dendritic cells and their impact on T-cell proliferation." PLoS One 4(3): e4946. Murphy, P. M., M. Baggiolini, et al. (2000). "International union of pharmacology. XXII. Nomenclature for chemokine receptors." Pharmacol Rev 52(1): 145-176. Oki, N., S. I. Takahashi, et al. (2000). "Short term feedback regulation of cAMP in FRTL-5 thyroid cells. Role of PDE4D3 phosphodiesterase activation." J Biol Chem 275(15): 10831-10837. Omori, K. and J. Kotera (2007). "Overview of PDEs and their regulation." Circ Res 100(3): 309-327. Patel, D. D., J. P. Zachariah, et al. (2001). "CXCR3 and CCR5 ligands in rheumatoid arthritis synovium." Clin Immunol 98(1): 39-45. Perry, M. J. and G. A. Higgs (1998). "Chemotherapeutic potential of phosphodiesterase inhibitors." Curr Opin Chem Biol 2(4): 472-481. Pozo, D., J. M. Guerrero, et al. (2002). "Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit LPS-stimulated MIP-1alpha production and mRNA expression." Cytokine 18(1): 35-42. Ramos, C. D., C. Canetti, et al. (2005). "MIP-1alpha[CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF-alpha and LTB4." J Leukoc Biol 78(1): 167-177. Rehmann, H., B. Prakash, et al. (2003). "Structure and regulation of the cAMP-binding domains of Epac2." Nat Struct Biol 10(1): 26-32. Rothenberg, M. E., N. Zimmermann, et al. (1999). "Chemokines and chemokine receptors: their role in allergic airway disease." J Clin Immunol 19(5): 250-265. Schafer, P. H., A. Parton, et al. (2010). "Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis." Br J Pharmacol 159(4): 842-855. Schnurr, M., T. Toy, et al. (2005). "Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway." Blood 105(4): 1582-1589. Sebastiani, S., P. Allavena, et al. (2001). "Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity." J Immunol 166(2): 996-1002. Shabb, J. B. (2001). "Physiological substrates of cAMP-dependent protein kinase." Chem Rev 101(8): 2381-2411. Sherry, B., P. Tekamp-Olson, et al. (1988). "Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta." J Exp Med 168(6): 2251-2259. Shirshev, S. V. (2011). "Role of Epac proteins in mechanisms of cAMP-dependent immunoregulation." Biochemistry (Mosc) 76(9): 981-998. Sodhi, A., S. Montaner, et al. (2004). "Viral hijacking of G-protein-coupled-receptor signalling networks." Nat Rev Mol Cell Biol 5(12): 998-1012. Souness, J. E., D. Aldous, et al. (2000). "Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors." Immunopharmacology 47(2-3): 127-162. Spina, D. (2008). "PDE4 inhibitors: current status." Br J Pharmacol 155(3): 308-315. Stanford, M. M. and T. B. Issekutz (2003). "The relative activity of CXCR3 and CCR5 ligands in T lymphocyte migration: concordant and disparate activities in vitro and in vivo." J Leukoc Biol 74(5): 791-799. Subbian, S., L. Tsenova, et al. (2011). "Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs." PLoS Pathog 7(9): e1002262. Takahashi, M., R. Terwilliger, et al. (1999). "Chronic antidepressant administration increases the expression of cAMP-specific phosphodiesterase 4A and 4B isoforms." J Neurosci 19(2): 610-618. Takayama, K., G. Garcia-Cardena, et al. (2002). "Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor." J Biol Chem 277(46): 44147-44154. Thivierge, M., C. Le Gouill, et al. (1998). "Prostaglandin E2 induces resistance to human immunodeficiency virus-1 infection in monocyte-derived macrophages: downregulation of CCR5 expression by cyclic adenosine monophosphate." Blood 92(1): 40-45. Tiwari, S., K. Felekkis, et al. (2004). Among circulating hematopoietic cells, B-CLL uniquely expresses functional EPAC1, but EPAC1-mediated Rap1 activation does not account for PDE4 inhibitor-induced apoptosis. Blood. 103: 2661-2667. Torphy, T. J. (1998). "Phosphodiesterase isozymes: molecular targets for novel antiasthma agents." Am J Respir Crit Care Med 157(2): 351-370. Tregoning, J. S., P. K. Pribul, et al. (2010). "The chemokine MIP1alpha/CCL3 determines pathology in primary RSV infection by regulating the balance of T cell populations in the murine lung." PLoS One 5(2): e9381. Usynin, I., C. Klotz, et al. (2007). "Malaria circumsporozoite protein inhibits the respiratory burst in Kupffer cells." Cell Microbiol 9(11): 2610-2628. Vaddi, K. and R. C. Newton (1994). "Regulation of monocyte integrin expression by beta-family chemokines." J Immunol 153(10): 4721-4732. van der Pouw Kraan, T. C., L. C. Boeije, et al. (1995). "Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production." J Exp Med 181(2): 775-779. Vang, T., K. M. Torgersen, et al. (2001). "Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor." J Exp Med 193(4): 497-507. Weedon-Fekjaer, M. S. and K. Tasken (2012). "Review: Spatiotemporal dynamics of hCG/cAMP signaling and regulation of placental function." Placenta 33 Suppl: S87-91. Weston, M. C., N. Anderson, et al. (1997). "Effects of phosphodiesterase inhibitors on human lung mast cell and basophil function." Br J Pharmacol 121(2): 287-295. Wolpe, S. D., G. Davatelis, et al. (1988). "Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties." J Exp Med 167(2): 570-581. Xiang, Y., F. Naro, et al. (2005). "Phosphodiesterase 4D is required for beta2 adrenoceptor subtype-specific signaling in cardiac myocytes." Proc Natl Acad Sci U S A 102(3): 909-914. Xu, X. J., J. S. Reichner, et al. (2008). "Prostaglandin E2 suppresses lipopolysaccharide-stimulated IFN-beta production." J Immunol 180(4): 2125-2131. Ying, S., Q. Meng, et al. (2001). "Macrophage inflammatory protein-1alpha and C-C chemokine receptor-1 in allergen-induced skin late-phase reactions: relationship to macrophages, neutrophils, basophils, eosinophils and T lymphocytes." Clin Exp Allergy 31(11): 1724-1731. Zeidler, R., M. Csanady, et al. (2000). "Tumor cell-derived prostaglandin E2 inhibits monocyte function by interfering with CCR5 and Mac-1." FASEB J 14(5): 661-668. Zlotnik, A. and O. Yoshie (2000). "Chemokines: a new classification system and their role in immunity." Immunity 12(2): 121-127.
指導教授	金秀蓮(Shiow-Lian Catherine Jin)	審核日期	2012-10-23
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