PDE4抑制劑與血清協同促進內毒素對巨噬細胞的移走作用

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：13

、訪客IP：3.149.230.44

姓名

翁福均(Fu-Chun Weng) 查詢紙本館藏

畢業系所

生命科學系

論文名稱

PDE4抑制劑與血清協同促進內毒素對巨噬細胞的移走作用
(Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated 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

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

[檢視]

[下載]

本電子論文使用權限為同意立即開放。
已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中)

巨噬細胞的移走作用是寄主對抗病原菌感染及修復受傷組織的必要免疫反應。已知cAMP專一性phosphodiesterase 4 (PDE4)是免疫細胞內主要水解cAMP的酵素，且在活化的巨噬細胞中，抑制PDE4以提升細胞內cAMP濃度，可抑制多種免疫發炎反應，進而減緩相關的發炎疾病。目前PDE4抑制劑的抗發炎作用已有較廣泛的報導，然而PDE4對巨噬細胞移走作用的調控仍知之甚少。為此，本研究使用格蘭氏陰性細菌外膜的lipopolysaccharide (LPS)刺激小鼠Raw 264.7巨噬細胞，並以傷口癒合試驗檢測PDE4抑制劑或cAMP對細胞移走的影響。結果顯示LPS會輕微地，但顯著地，誘導巨噬細胞移走，而PDE4抑制劑rolipram會大幅提升此作用，此外，巨噬細胞移走也會隨著rolipram濃度上升而逐漸增加。我們發現rolipram提升的移走作用需要血清的參與，因為在無血清培養下此提升作用不會產生。進一步以不同濃度的牛胎血清(0、2、10% FBS)處理細胞，結果顯示，rolipram與血清能協同促進LPS所誘導的巨噬細胞移走。此外，小鼠與馬血清也具有相同的協同作用，這表示在哺乳動物的血清中，可能有共同的因子會與rolipram協同促進LPS誘導巨噬細胞的移走。實驗進一步證實此rolipram作用是經由活化exchange proteins directly activated by cAMP (Epac)，而非protein kinase A的訊息傳導路徑所致，我們推測這是在血清因子的影響下，由cAMP/Epac訊息傳導與LPS/TLR4訊息傳導的交互作用所引起的移走作用。這些結果表明，隨同血清因子的參與，PDE4抑制劑能促使巨噬細胞被招募至發炎部位，以致更有效的清除病原體及修復傷口。

摘要(英)

Macrophage migration is an essential step in host defense against infection and wound healing. Elevation of cAMP by inhibiting phosphodiesterase 4 (PDE4), enzymes that specifically degrade cAMP, is known to suppress various inflammatory responses in activated macrophages, but the role of PDE4 in macrophage migration is poorly understood. Here we show that the migration of Raw 264.7 macrophages stimulated with LPS was markedly and dose-dependently induced by the PDE4 inhibitor rolipram as assessed by scratch wound healing assay. Additionally, this response required the involvement of serum in the culture medium as serum starvation abrogated the effect. Further analysis revealed that rolipram and serum exhibited synergistic effect on the migration. Moreover, the enhanced migration by rolipram was mediated by activating cAMP/exchange proteins directly activated by cAMP (Epac) signaling, presumably via interaction with LPS/TLR4 signaling with the participation of unknown serum components. These results suggest that PDE4 inhibitors, together with serum components, may serve as positive regulators of macrophage recruitment for more efficient pathogen clearance and wound repair.

關鍵字(中)

★ 環核苷酸磷酸二酯酶4
★ 巨噬細胞
★ 環腺苷酸
★ 血清
★ 移走作用

關鍵字(英)

★ phosphodiesterase 4
★ macrophage
★ cAMP
★ serum
★ migration

論文目次

中文摘要 …………………………………………………………………………… i
英文摘要 …………………………………………………………………………… ii
目錄 …………………………………………………………………………… iii
圖目錄 …………………………………………………………………………… v
縮寫檢索表 …………………………………………………………………………… vi
一、緒論 ………………………………………………………………… 1
1-1 巨噬細胞的生理功能 ……………………………………… 1
1-2 巨噬細胞的移走作用 ……………………………………… 2
1-3 脂多醣 (lipopolysaccharide, LPS)對巨噬細胞移走的影響 ………………………………………………………………………………………………………………………… 3
1-4 cAMP對細胞移走的影響 ……………………………………………… 4
1-5 cAMP的訊息傳導路徑 …………………………………………………… 5
1-6 環狀核苷酸磷酸二酯酶(Cyclic nucleotide phosphodiesterase, PDE)…………………………………………………………… 6
1-7 PDE4家族………………………………………………………………………………… 8
1-8 PDE4與巨噬細胞的功能調控…………………………………………… 9
二、研究動機與目的…………………………………………………………………… 11
三、材料與方法……………………………………………………………………………… 12
3-1 實驗材料 ………………………………………………………………………………… 12
3-1-1 實驗細胞株……………………………………………………………………………… 12
3-1-2 細胞培養液……………………………………………………………………………… 12
3-1-3 化學藥品…………………………………………………………………………………… 12
3-1-4 細胞攝影及分析軟體…………………………………………………………… 13
3-2 實驗方法 ………………………………………………………………………………… 13
3-2-1 小鼠Raw 264.7巨噬細胞培養 ……………………………………… 13
3-2-2 傷口癒合試驗(Wound healing assay)…………………… 13
3-2-3 傷口面積定量…………………………………………………………………………… 13
3-2-4 血清與藥物處理Raw 264.7巨噬細胞 ………………………… 13
3-2-5 Raw 264.7巨噬細胞移走分析 ……………………………………… 14
3-2-6 MTT細胞存活檢測(MTT assay) …………………………………… 14
四、實驗結果 ………………………………………………………………………………… 15
4-1 PDE4抑制劑對LPS誘導巨噬細胞移走的影響 …………… 15
4-2 抑制PDE4以增加cAMP可促進LPS誘導巨噬細胞移走…… 16
4-3 PDE4抑制劑roflumilast亦可加強LPS對巨噬細胞的移走作用 ………………………………………………………………………………………………………………………………… 17
4-4 血清對於PDE4抑制劑提升LPS誘導巨噬細胞移走的影響 …… 17
4-5 Rolipram與血清可協同促進LPS誘導巨噬細胞移走……………… 18
4-6 小鼠血清或馬血清亦可協同rolipram促進LPS誘導巨噬細胞移走………………………………………………………………………………………………………………………………………… 19
4-7 PKA不參與PDE4抑制劑提升巨噬細胞的移走作用 ………………… 19
4-8 PDE4抑制劑提升LPS誘導巨噬細胞移走是經由活化Epac訊息傳導………………………………………………………………………………………………………………………………………… 20
五、討論 …………………………………………………………………………………………… 21
六、圖與圖解 ……………………………………………………………………………………… 25
參考文獻 …………………………………………………………………………………………………… 34
附圖 ……………………………………………………………………………………………………………… 45

參考文獻

Aderem, A. and D. M. Underhill (1999). "Mechanisms of phagocytosis in macrophages." Annual Review of Immunology 17(1): 593-623.
Akira, S., et al. (2001). "Toll-like receptors: critical proteins linking innate and acquired immunity." Nature Immunology 2: 675.
Alves, A. C., et al. (1996). "Selective inhibition of phosphodiesterase type IV suppresses the chemotactic responsiveness of rat eosinophils in vitro." European journal of pharmacology 312(1): 89-96.
Aronoff, D. M., et al. (2005). "Cutting edge: Macrophage inhibition by cyclic AMP (cAMP): Differential roles of protein kinase A and exchange protein directly activated by cAMP-1." The Journal of Immunology 174(2): 595.
Aronoff, D. M., et al. (2006). "Short communication: Differences between macrophages and dendritic cells in the cyclic AMP-dependent regulation of lipopolysaccharide-induced cytokine and chemokine synthesis." Journal of Interferon & Cytokine Research 26(11): 827-833.
Asirvatham, A. L., et al. (2004). "A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines." The Journal of Immunology 173(8): 4806-4814.
Banerjee, S., et al. (2015). "RNase L is a negative regulator of cell migration." Oncotarget 6(42): 44360-44372.
Beard, M. B., et al. (2000). "UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions." Journal of Biological Chemistry 275(14): 10349-10358.
Beavo, J. A. and L. L. Brunton (2002). "Cyclic nucleotide research—still expanding after half a century." Nature reviews Molecular cell biology 3(9): 710.
Bhushan, S., et al. (2009). "Testicular innate immune defense against bacteria." Molecular and Cellular Endocrinology 306(1): 37-44.
Bos, J. L. (2006). "Epac proteins: multi-purpose cAMP targets." Trends in biochemical sciences 31(12): 680-686.
Brand, T. and R. Schindler (2017). "New kids on the block: The popeye domain containing (Popdc) protein family acting as a novel class of cAMP effector proteins in striated muscle." Cellular signalling 40: 156-165.
Brink, H. E., et al. (2006). "Serum-dependent effects on adult and fetal tendon fibroblast migration and collagen expression." Wound Repair and Regeneration 14(2): 179-186.
Burdyga, A., et al. (2013). "cAMP inhibits migration, ruffling and paxillin accumulation in focal adhesions of pancreatic ductal adenocarcinoma cells: effects of PKA and EPAC." Biochimica et biophysica acta 1833(12): 2664-2672.
Cedervall, P., et al. (2015). "Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4." Proceedings of the National Academy of Sciences: 201419906.
Chen, L., et al. (2008). "cAMP inhibits cell migration by interfering with Rac-induced lamellipodium formation." Journal of Biological Chemistry 283(20): 13799-13805.
CHIN, K. V., et al. (2002). "Reinventing the wheel of cyclic AMP." Annals of the New York Academy of Sciences 968(1): 49-64.
Chung, K. F. (2006). "Phosphodiesterase inhibitors in airways disease." European journal of pharmacology 533(1-3): 110-117.
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.
Daley, J. M., et al. (2010). "The phenotype of murine wound macrophages." Journal of leukocyte biology 87(1): 59-67.
de Rooij, J., et al. (1998). "Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP." Nature 396: 474.
Dell’Acqua, M. L. and J. D. Scott (1997). "Protein kinase A anchoring." Journal of Biological Chemistry 272(20): 12881-12884.
Etxebarria, J., et al. (2017). "Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness." Acta Ophthalmologica 95(8): e693-e705.
Fleming, Y. M., et al. (2004). "PDE4-regulated cAMP degradation controls the assembly of integrin-dependent actin adhesion structures and REF52 cell migration." Journal of Cell Science 117(11): 2377.
Fukata, M., et al. (2009). "Innate immune signaling by Toll-like receptor-4 (TLR4) shapes the inflammatory microenvironment in colitis-associated tumors." Inflammatory bowel diseases 15(7): 997-1006.
Furundzija, V., et al. (2010). "IGF-1 increases macrophage motility via PKC/p38-dependent αvβ3-integrin inside-out signaling." Biochemical and Biophysical Research Communications 394(3): 786-791.
Gentek, R., et al. (2014). "Tissue macrophage identity and self‐renewal." Immunological reviews 262(1): 56-73.
Gloerich, M. and J. L. Bos (2010). "Epac: defining a new mechanism for cAMP action." Annual review of pharmacology toxicology 50: 355-375.
Goc, A., et al. (2010). "Structural characterization of the rod cGMP phosphodiesterase 6." Journal of molecular biology 401(3): 363-373.
Grandoch, M., et al. (2009). "Epac inhibits migration and proliferation of human prostate carcinoma cells." British journal of cancer 101(12): 2038-2042.
Gregory, S. H., et al. (2002). "Complementary adhesion molecules promote neutrophil-Kupffer cell interaction and the elimination of bacteria taken up by the liver." The Journal of Immunology 168(1): 308-315.
Hesketh, M., et al. (2017). "Macrophage phenotypes regulate scar formation and chronic wound healing." International journal of molecular sciences 18(7): 1545.
Hu, X., et al. (2008). "Regulation of interferon and Toll‐like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms." Immunological reviews 226(1): 41-56.
Imhof, B. A. and M. Aurrand-Lions (2004). "Adhesion mechanisms regulating the migration of monocytes." Nature Reviews Immunology 4(6): 432.
Jin, S., et al. (2012). "Phosphodiesterase 4 and its inhibitors in inflammatory diseases." Chang Gung Med J 35(3): 197-210.
Jin, S.-L., et al. (1992). "Characterization of the structure of a low Km, rolipram-sensitive cAMP phosphodiesterase. Mapping of the catalytic domain." Journal of Biological Chemistry 267(26): 18929-18939.
Jin, S.-L. C., et al. (2005). "Specific role of phosphodiesterase 4B in lipopolysaccharide-induced signaling in mouse macrophages." The Journal of Immunology 175(3): 1523-1531.
Junt, T., et al. (2007). "Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells." Nature 450(7166): 110.
Kaufman, L. M. and J. N. Barrett (1983). "Serum factor supporting long-term survival of rat central neurons in culture." Science 220(4604): 1394.
Kaupp, U. B. and R. Seifert (2002). "Cyclic nucleotide-gated ion channels." Physiological reviews 82(3): 769-824.
Kawai, T. and S. Akira (2010). "The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors." Nature Immunology 11: 373.
Kawasaki, H., et al. (1998). "A family of cAMP-binding proteins that directly activate Rap1." Science 282(5397): 2275-2279.
Kim, J.-S., et al. (2006). "Transforming growth factor-β1 regulates macrophage migration via RhoA." Blood 108(6): 1821.
Kim, M. O., et al. (2015). "cAMP promotes cell migration through cell junctional complex dynamics and actin cytoskeleton remodeling: Implications in skin wound healing." Stem cells development 24(21): 2513-2524.
Kim, S.-Y., et al. (2010). "Role of NADPH oxidase-2 in lipopolysaccharide-induced matrix metalloproteinase expression and cell migration." Immunology & Cell Biology 88(2): 197-204.
Kohyama, T., et al. (2004). "Cytokines modulate cilomilast response in lung fibroblasts." Clinical Immunology 111(3): 297-302.
Kopydlowski, K. M., et al. (1999). "Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo." The Journal of Immunology 163(3): 1537.
Krähling, A. M., et al. (2013). "CRIS—a novel cAMP-binding protein controlling spermiogenesis and the development of flagellar bending." PLoS genetics 9(12): e1003960.
Krettek, A., et al. (2001). "Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages: Influence of IFN-γ and TGF-β." Atherosclerosis 156(2): 267-275.
Kumar, N., et al. (2013). "Phosphodiesterase 4-targeted treatments for autoimmune diseases." BMC medicine 11: 96-96.
Lai, C.-R., et al. (2015). "Phosphodiesterase 4B is essential for lipopolysaccharide-induced CC chemokine ligand 3 production in mouse macrophages." Journal of Medical Sciences 35(3): 111-119.
Lauffenburger, D. A. and A. F. Horwitz (1996). "Cell migration: a physically integrated molecular process." cell 84(3): 359-369.
Layseca-Espinosa, E., et al. (2003). "Rolipram Inhibits polarization and migration of human T lymphocytes." Journal of Investigative Dermatology 121(1): 81-87.
LENHARD, J. M., et al. (1996). "Phosphorylation of a cAMP-specific phosphodiesterase (HSPDE4B2B) by mitogen-activated protein kinase." Biochemical Journal 316(3): 751-758.
Lichtman, S. N., et al. (1998). "LPS receptor CD14 participates in release of TNF-α in RAW 264.7 and peritoneal cells but not in Kupffer cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 275(1): G39-G46.
Lorenowicz, M. J., et al. (2008). "PKA and Epac1 regulate endothelial integrity and migration through parallel and independent pathways." European journal of cell biology 87(10): 779-792.
Martinez, S. E., et al. (2002). "The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding." Proceedings of the National Academy of Sciences 99(20): 13260-13265.
Matthiesen, K. and J. Nielsen (2009). "Binding of cyclic nucleotides to phosphodiesterase 10A and 11A GAF domains does not stimulate catalytic activity." Biochemical Journal 423(3): 401-409.
Maurice, D. H., et al. (2014). "Advances in targeting cyclic nucleotide phosphodiesterases." Nature reviews. Drug discovery 13(4): 290-314.
McKean, J. S., et al. (2015). "The cAMP-producing agonist beraprost inhibits human vascular smooth muscle cell migration via exchange protein directly activated by cAMP." Cardiovascular research 107(4): 546-555.
Mebius, R. E. and G. Kraal (2005). "Structure and function of the spleen." Nature Reviews Immunology 5(8): 606.
Michaud, J., et al. (2010). "Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during inflammation." Journal of immunology (Baltimore, Md. : 1950) 184(3): 1475-1483.
Moon, M.-Y., et al. (2013). "Small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-β1." Journal of Cellular Physiology 228(11): 2119-2126.
Mou, H. and R. H. Cote (2001). "The catalytic and GAF domains of the rod cGMP phosphodiesterase (PDE6) heterodimer are regulated by distinct regions of its inhibitory γ subunit." Journal of Biological Chemistry 276(29): 27527-27534.
Muradov, H., et al. (2004). "Structural determinants of the PDE6 GAF A domain for binding the inhibitory γ-subunit and noncatalytic cGMP." Vision research 44(21): 2437-2444.
Murray, M. Y., et al. (2013). "Macrophage migration and invasion is regulated by MMP10 expression." PloS one 8(5): e63555-e63555.
Murray, P. J. and T. A. Wynn (2011). "Protective and pathogenic functions of macrophage subsets." Nature Reviews Immunology 11(11): 723.
Netherton, S. J. and D. H. Maurice (2005). "Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell migration: Implications in angiogenesis." Molecular Pharmacology 67(1): 263.
Ohto, U., et al. (2007). "Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa." Science 316(5831): 1632.
Omori, K. and J. Kotera (2007). "Overview of PDEs and their regulation." Circulation research 100(3): 309-327.
Panzer, U. and M. Uguccioni (2004). "Prostaglandin E2 modulates the functional responsiveness of human monocytes to chemokines." European journal of immunology 34(12): 3682-3689.
Petrie, R. J., et al. (2009). "Random versus directionally persistent cell migration." Nature reviews Molecular cell biology 10: 538.
Pollard, J. W. (2009). "Trophic macrophages in development and disease." Nature reviews. Immunology 9(4): 259-270.
Poole, N. M., et al. (2013). "Prostaglandin E(2) in tick saliva regulates macrophage cell migration and cytokine profile." Parasites & vectors 6(1): 261-261.
Porpodis, K., et al. (2015). "Roflumilast, a phosphodiesterase-4 inhibitor, induces phagocytic activity in Greek COPD patients." International journal of chronic obstructive pulmonary disease 10: 1123-1128.
Prabhakar, U., et al. (1994). "Characterization of cAMP-dependent inhibition of LPS-induced TNFα production by rolipram, a specific phosphodiesterase IV (PDE IV) inhibitor." International Journal of Immunopharmacology 16(10): 805-816.
Richter, W. and M. Conti (2002). "Dimerization of the type 4 cAMP-specific phosphodiesterases is mediated by the upstream conserved regions (UCRs)." Journal of Biological Chemistry.
Ridley, A. J. (2001). "Rho proteins, PI 3‐kinases, and monocyte/macrophage motility." FEBS letters 498(2-3): 168-171.
Ridley, A. J., et al. (2003). "Cell migration: integrating signals from front to back." Science 302(5651): 1704-1709.
Ring, S., et al. (2015). "Regulatory T cell–derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway." The Journal of Immunology 194(8): 3735.
Rybalkin, S. D., et al. (2003). "PDE5 is converted to an activated state upon cGMP binding to the GAF A domain." The EMBO Journal 22(3): 469-478.
Sandulache, V. C., et al. (2007). "Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-β1–induced collagen synthesis." Wound Repair and Regeneration 15(1): 122-133.
Santamaria, L. F., et al. (1997). "Inhibition of eotaxin-mediated human eosinophil activation and migration by the selective cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram." British journal of pharmacology 121(6): 1150-1154.
Schafer, P. H., et al. (2016). "Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex." Cellular signalling 28(7): 753-763.
Schudt, C., et al. (1995). "PDE isoenzymes as targets for anti-asthma drugs." European Respiratory Journal 8(7): 1179-1183.
Schumann, R. R., et al. (1990). "Structure and function of lipopolysaccharide binding protein." Science 249(4975): 1429.
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.
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.
Shabb, J. B. (2001). "Physiological substrates of cAMP-dependent protein kinase." Chemical reviews 101(8): 2381-2412.
Shi, C. and E. G. Pamer (2011). "Monocyte recruitment during infection and inflammation." Nature Reviews Immunology 11(11): 762.
Soderling, S. H., et al. (1999). "Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A." Proceedings of the National Academy of Sciences 96(12): 7071-7076.
Tajima, T., et al. (2008). "Lipopolysaccharide induces macrophage migration via prostaglandin D2 and prostaglandin E2." Journal of Pharmacology Experimental Therapeutics 326(2): 493-501.
Unanue, E. R. and P. M. Allen (1987). "The basis for the immunoregulatory role of macrophages and other accessory cells." Science 236(4801): 551-557.
Veale, K. J., et al. (2010). "Recycling endosome membrane incorporation into the leading edge regulates lamellipodia formation and macrophage migration." Traffic 11(10): 1370-1379.
Wang, J., et al. (2013). "Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1." Arthritis and rheumatism 65(3): 832-842.
Wang, P., et al. (2003). "Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5): differential tissue distribution and subcellular localization of PDE9A variants." Gene 314: 15-27.
Weeks, J. L., et al. (2007). "N-Terminal domain of phosphodiesterase-11A4 (PDE11A4) decreases affinity of the catalytic site for substrates and tadalafil, and is involved in oligomerization." Biochemistry 46(36): 10353-10364.
West, A. P., et al. (2006). "Recognition and signaling by Toll-like receptors." Annual Review of Cell and Developmental Biology 22(1): 409-437.
Wright, S. D., et al. (1990). "CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein." Science 249(4975): 1431.
Wu, P. and P. Wang (2004). "Per-Arnt-Sim domain-dependent association of cAMP-phosphodiesterase 8A1 with IκB proteins." Proceedings of the National Academy of Sciences of the United States of America 101(51): 17634-17639.
Wynn, T. A., et al. (2013). "Macrophage biology in development, homeostasis and disease." Nature 496(7446): 445.
Yang, J.-X., et al. (2017). "Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages." Scientific reports 7: 46165-46165.
Yang, Y. H., et al. (2015). "Acetylcholine inhibits LPS-induced MMP-9 production and cell migration via the a7 nAChR-JAK2/STAT3 pathway in RAW264.7 cells." Cellular Physiology and Biochemistry 36(5): 2025-2038.
Yokoyama, U., et al. (2008). "Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A." The Journal of biological chemistry 283(42): 28702-28709.
Zhang, X. and D. Mosser (2008). "Macrophage activation by endogenous danger signals." The Journal of Pathology 214(2): 161-178.
Zimmerman, N. P., et al. (2012). "Cyclic AMP dysregulates intestinal epithelial cell restitution through PKA and RhoA." Inflammatory bowel diseases 18(6): 1081-1091.
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

審核日期

2019-3-29

推文