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Cyclic Nucleotides and Phosphodiesterases in Monocytic Differentiation

  • Angie L. Hertz
  • Joseph A. BeavoEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 204)

Abstract

Monocytes are immune cells that can differentiate into a number of cell types including macrophages, dendritic cells, and osteoclasts upon exposure to various cytokines. The phenotypes of these differentiated cells are highly heterogeneous and their differentiation can be affected by the cyclic nucleotides, 3′-5′-cyclic adenosine monophosphate (cAMP) and 3′-5′-cyclic guanosine monophosphate (cGMP). The intracellular levels of cAMP and cGMP are controlled through regulation of production by adenylyl and guanylyl cyclases and through degradation by cyclic nucleotide phosphodiesterases (PDEs). PDE inhibition and subsequent changes in cyclic nucleotide levels can alter the final phenotype of a differentiating monocyte with regards to surface marker expression, gene expression, or changes in secreted chemokine and cytokine levels. The differentiation process itself can also be either inhibited or augmented by changes in cyclic nucleotide levels, depending on the system being studied and the timing of cyclic nucleotide elevation. This chapter explores the effects of PDE inhibition and increases in cGMP and cAMP on monocytic differentiation into osteoclasts, dendritic cells, and macrophages.

Keywords

Bone-marrow derived macrophage Dendritic cell Macrophage Monocyte Osteoclast 

References

  1. Addi Abduelhakem B, Lefort A, Hua X, Libert F, Communi D, Ledent C, Macours P, Tilley SL, Boeynaems J-M, Robaye B (2008) Modulation of murine dendritic cell function by adenine nucleotides and adenosine: involvement of the A2B receptor. Eur J Immunol 38:1610–1620PubMedCrossRefGoogle Scholar
  2. Baillie GS, MacKenzie SJ, McPhee I, Houslay MD (2000) Sub-family selective actions in the ability of Erk2 MAP kinase to phosphorylate and regulate the activity of PDE4 cyclic AMP-specific phosphodiesterases. Br J Pharmacol 131:811–819PubMedCrossRefGoogle Scholar
  3. Bang B, Ericsen C, Aarbakke J (1994) Effects of cAMP and cGMP elevating agents on HL-60 cell differentiation. Pharmacol Toxicol 75:108–112PubMedCrossRefGoogle Scholar
  4. Bar-Shavit Z (2007) The osteoclast: a multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell. J Cell Biochem 102:1130–1139PubMedCrossRefGoogle Scholar
  5. Bender AT, Beavo JA (2004) Specific localized expression of cGMP PDEs in Purkinje neurons and macrophages. Neurochem Int 45:853–857PubMedCrossRefGoogle Scholar
  6. Bender AT, Beavo JA (2006a) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488–520PubMedCrossRefGoogle Scholar
  7. Bender AT, Beavo JA (2006b) PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte. Proc Natl Acad Sci USA 103:460–465PubMedCrossRefGoogle Scholar
  8. Bender AT, Ostenson CL, Giordano D, Beavo JA (2004) Differentiation of human monocytes in vitro with granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor produces distinct changes in cGMP phosphodiesterase expression. Cell Signal 16:365–374PubMedCrossRefGoogle Scholar
  9. Bender AT, Ostenson CL, Wang EH, Beavo JA (2005) Selective up-regulation of PDE1B2 upon monocyte-to-macrophage differentiation. Proc Natl Acad Sci USA 102:497–502PubMedCrossRefGoogle Scholar
  10. Boeynaems J-M, Communi D, Savi P, Herbert J-M (2000) P2Y receptors: in the middle of the road. Trends Pharmacol Sci 21:1–3PubMedCrossRefGoogle Scholar
  11. Bornfeldt KE (2006) A single second messenger: several possible cellular responses depending on distinct subcellular pools. Circ Res 99:790–792PubMedCrossRefGoogle Scholar
  12. Boss G (1989) cGMP-induced differentiation of the promyelocytic cell line HL-60. Proc Natl Acad Sci USA 86:7174–7178PubMedCrossRefGoogle Scholar
  13. Brodsky A, Davio C, Shayo C, Lemos Legnazzi B, Barbosa M, Lardo M, Morelli A, Baldi A, Sanchez Avalos JC, Rivera E (1998) Forskolin induces U937 cell line differentiation as a result of a sustained cAMP elevation. Eur J Pharmacol 350:121–127PubMedCrossRefGoogle Scholar
  14. Bryn T, Mahic M, Enserink JM, Schwede F, Aandahl EM, Tasken K (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 176:7361–7370PubMedGoogle Scholar
  15. Burke B, Sumner S, Maitland N, Lewis CE (2002) Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. J Leukoc Biol 72:417–428PubMedGoogle Scholar
  16. Chaplinski TJ, Niedel JE (1982) Cyclic nucleotide-induced maturation of human promyelocytic leukemia cells. J Clin Invest 70:953–964PubMedCrossRefGoogle Scholar
  17. Cho Y-J, Kim J-Y, Jeong S-W, Lee SB, Kim ON (2003) Cyclic AMP induces activation of extracellular signal-regulated kinases in HL-60 cells: role in cAMP-induced differentiation. Leuk Res 27:51–56PubMedCrossRefGoogle Scholar
  18. Cho E, Yu J, Kim M, Yim M (2004) Rolipram, a phosphodiesterase 4 inhibitor, stimulates osteoclast formation by inducing TRANCE expression in mouse calvarial cells. Arch Pharm Res 27:1258–1262PubMedCrossRefGoogle Scholar
  19. Conti M, Richter W, Mehats C, Livera G, Park J-Y, Jin C (2003) Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling. J Biol Chem 278:5493–5496PubMedCrossRefGoogle Scholar
  20. Essayan DM (2001) Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 108:671–680PubMedCrossRefGoogle Scholar
  21. Fernandez N, Monczor F, Lemos B, Notcovich C, Baldi A, Davio C, Shayo C (2002) Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation. Mol Pharmacol 62:1506–1514PubMedCrossRefGoogle Scholar
  22. Fidock M, Miller M, Lanfear J (2002) Isolation and differential tissue distribution of two human cDNAs encoding PDE1 splice variants. Cell Signal 14:53–60PubMedCrossRefGoogle Scholar
  23. Fischmeister R, Castro LRV, Abi-Gerges A, Rochais F, Jurevicius J, Leroy J, Vandecasteele G (2006) Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res 99:816–828PubMedCrossRefGoogle Scholar
  24. Fujita D, Yamashita N, Iita S, Amano H, Yamada S, Sakamoto K (2003) Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells. Prostaglandins Leukot Essent Fatty Acids 68:351–358PubMedCrossRefGoogle Scholar
  25. Gantner F, Kupferschmidt R, Schudt C, Wendel A, Hatzelmann A (1997a) In vitro differentiation of human monocytes to macrophages: change of PDE profile and its relationship to suppression of tumour necrosis factor-[alpha] release by PDE inhibitors. Br J Pharmacol 121:221–231PubMedCrossRefGoogle Scholar
  26. Gantner F, Tenor H, Gekeler V, Schudt C, Wendel A, Hatzelmann A (1997b) Phosphodiesterase profiles of highly purified human peripheral blood leukocyte populations from normal and atopic individuals: a comparative study. J Allergy Clin Immunol 100:527–535PubMedCrossRefGoogle Scholar
  27. Gantner F, Schudt C, Wendel A, Hatzelmann A (1999) Characterization of the phosphodiesterase (PDE) pattern of in vitro-generated human dendritic cells (DC) and the influence of PDE inhibitors on DC function. Pulm Pharmacol Ther 12:377–386PubMedCrossRefGoogle Scholar
  28. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K (2010) Development of monocytes, macrophages, and dendritic cells. Science 327:656–661PubMedCrossRefGoogle Scholar
  29. Gilchrist M, Thorsson V, Li B, Rust AG, Korb M, Kennedy K, Hai T, Bolouri H, Aderem A (2006) Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441:173–178PubMedCrossRefGoogle Scholar
  30. Giordano D, Magaletti DM, Clark EA, Beavo JA (2003) Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cells. J Immunol 171:6421–6430PubMedGoogle Scholar
  31. Grage-Griebenow E, Flad HD, Ernst M (2001) Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol 69:11–20PubMedGoogle Scholar
  32. Harris P, Ralph P (1985) Human leukemic models of myelomonocytic development: a review of the HL-60 and U937 cell lines. J Leukoc Biol 37:407–422PubMedGoogle Scholar
  33. Haskó G, Csóka B, Németh ZH, Vizi ES, Pacher P (2009) A2B adenosine receptors in immunity and inflammation. Trends Immunol 30:263–270PubMedCrossRefGoogle Scholar
  34. Hertz AL, Bender AT, Smith KC, Gilchrist M, Amieux PS, Aderem A, Beavo JA (2009a) Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages. Proc Natl Acad Sci USA. doi: 10.1073/pnas.0911684106 PubMedGoogle Scholar
  35. Hertz AL, Bender AT, Smith KC, Gilchrist M, Amieux PS, Aderem A, Beavo JA (2009b) Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages. Proc Natl Acad Sci 106:21978–21983PubMedCrossRefGoogle Scholar
  36. Heystek HC, Thierry A-C, Soulard P, Moulon C (2003) Phosphodiesterase 4 inhibitors reduce human dendritic cell inflammatory cytokine production and Th1-polarizing capacity. Int Immunol 15:827–835PubMedCrossRefGoogle Scholar
  37. Holliday LS, Dean AD, Lin RH, Greenwald JE, Gluck SL (1997) Low NO concentrations inhibit osteoclast formation in mouse marrow cultures by cGMP-dependent mechanism. Am J Physiol Renal Physiol 272:F283–F291Google Scholar
  38. Houslay MD (2010) Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem Sci 35:91–100PubMedCrossRefGoogle Scholar
  39. Houslay MD, Schafer P, Zhang KYJ (2005) Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 10:1503–1519PubMedCrossRefGoogle Scholar
  40. Itonaga I, Sabokbar A, Neale SD, Athanasou NA (1999) 1, 25-Dihydroxyvitamin D3 and prostaglandin E2 act directly on circulating human osteoclast precursors. Biochem Biophys Res Comm 264:590–595PubMedCrossRefGoogle Scholar
  41. Jiang L, Foster FM, Ward P, Tasevski V, Luttrell BM, Conigrave AD (1997) Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells. Biochem Biophys Res Comm 232:626–630PubMedCrossRefGoogle Scholar
  42. Jonuleit H, Kühn U, Müller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk A (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27:3135–3142PubMedCrossRefGoogle Scholar
  43. Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML (1997) IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 159:28–35PubMedGoogle Scholar
  44. Kalinski P, Schuitemaker JHN, Hilkens CMU, Kapsenberg ML (1998) Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: the levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol 161:2804–2809PubMedGoogle Scholar
  45. Kinoshita T, Kobayashi S, Ebara S, Yoshimura Y, Horiuchi H, Tsutsumimoto T, Wakabayashi S, Takaoka K (2000) Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice. Bone 27:811–817PubMedCrossRefGoogle Scholar
  46. Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, Marder JB, Yoles E, Belkin M, Schwartz M, Hadani M (2005) Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine 3:173–181PubMedCrossRefGoogle Scholar
  47. Kobayashi Y, Mizoguchi T, Take I, Kurihara S, Udagawa N, Takahashi N (2005a) Prostaglandin E2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK1. J Biol Chem 280:11395–11403PubMedCrossRefGoogle Scholar
  48. Kobayashi Y, Take I, Yamashita T, Mizoguchi T, Ninomiya T, Hattori T, Kurihara S, Ozawa H, Udagawa N, Takahashi N (2005b) Prostaglandin E2 receptors EP2 and EP4 are down-regulated during differentiation of Mouse osteoclasts from their precursors. J Biol Chem 280:24035–24042PubMedCrossRefGoogle Scholar
  49. Kurland JI, Hadden JW, Moore MAS (1977) Role of cyclic nucleotides in the proliferation of committed granulocyte-macrophage progenitor cells. Cancer Res 37:4534–4538PubMedGoogle Scholar
  50. Kurland J, Bockman R, Broxmeyer H, Moore M (1978a) Limitation of excessive myelopoiesis by the intrinsic modulation of macrophage-derived prostaglandin E. Science 199:552PubMedCrossRefGoogle Scholar
  51. Kurland J, Broxmeyer H, Pelus M, Bockman R, Moore M (1978b) Role for monocyte-macrophage-derived colony stimulating factor and prostaglandin E in the positive and negative feedback control of myeloid stem cell proliferation. Blood 52:388PubMedGoogle Scholar
  52. Legnazzi BL, Shayo C, Monczor F, Martin ME, Fernandez N, Brodsky A, Baldi A, Davio C (2000) Rapid desensitization and slow recovery of the cyclic AMP response mediated by histamine H2 receptors in the U937 cell line. Biochem Pharmacol 60:159–166CrossRefGoogle Scholar
  53. Li X, Okada Y, Pilbeam CC, Lorenzo JA, Kennedy CRJ, Breyer RM, Raisz LG (2000) Knockout of the murine prostaglandin EP2 receptor impairs osteoclastogenesis in vitro. Endocrinology 141:2054–2061PubMedCrossRefGoogle Scholar
  54. Luft T, Jefford M, Luetjens P, Toy T, Hochrein H, Masterman K-A, Maliszewski C, Shortman K, Cebon J, Maraskovsky E (2002) Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets. Blood 100:1362–1372PubMedCrossRefGoogle Scholar
  55. Mano M, Arakawa T, Mano H, Nakagawa M, Kaneda T, Kaneko H, Yamada T, Miyata K, Kiyomura H, Kumegawa M, Hakeda Y (2000) Prostaglandin E2 directly inhibits bone-resorbing activity of isolated mature osteoclasts mainly through the EP4 receptor. Calcif Tissue Int 67:85–92PubMedCrossRefGoogle Scholar
  56. Miyamoto K-i, Waki Y, Horita T, Kasugai S, Ohya K (1997) Reduction of bone loss by denbufylline, an inhibitor of phosphodiesterase 4. Biochem Pharmacol 54:613–617PubMedCrossRefGoogle Scholar
  57. Miyamoto K-i, Nishioka T, Waki Y, Nomura M, Katsuta H, Yokogawa K, Amano H (2006) Phosphodiesterase 4 inhibitor rolipram potentiates the inhibitory effect of calcitonin on osteoclastogenesis. J Bone Miner Metab 24:260–265PubMedCrossRefGoogle Scholar
  58. Monczor F, Fernandez N, Riveiro E, Mladovan A, Baldi A, Shayo C, Davio C (2006) Histamine H2 receptor overexpression induces U937 cell differentiation despite triggered mechanisms to attenuate cAMP signalling. Biochem Pharmacol 71:1219–1228PubMedCrossRefGoogle Scholar
  59. Morelli AE, Thomson AW (2003) Dendritic cells under the spell of prostaglandins. Trends Immunol 24:108–111PubMedCrossRefGoogle Scholar
  60. Morita R, Ukyo N, Furuya M, Uchiyama T, Hori T (2003) Atrial natriuretic peptide polarizes human dendritic cells toward a Th2-promoting phenotype through its receptor guanylyl cyclase-coupled receptor A. J Immunol 170:5869–5875PubMedGoogle Scholar
  61. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969PubMedCrossRefGoogle Scholar
  62. Nakashima T, Takayanagi H (2009) Osteoclasts and the immune system. J Bone Miner Metab 27:519–529PubMedCrossRefGoogle Scholar
  63. Noh ALSM, Yang M, Lee J-M, Park H, Lee D-S, Yim M (2009) Phosphodiesterase 3 and 4 negatively regulate receptor activator of nuclear factor-kappa B ligand-mediated osteoclast formation by prostaglandin E2. Biol Pharm Bull 32:1844–1848PubMedCrossRefGoogle Scholar
  64. Nonaka T, Mio M, Doi M, Tasaka K (1992) Histamine-induced differentiation of HL-60 cells: the role of cAMP and protein kinase A. Biochem Pharmacol 44:1115–1121PubMedCrossRefGoogle Scholar
  65. Novitskiy SV, Ryzhov S, Zaynagetdinov R, Goldstein AE, Huang Y, Tikhomirov OY, Blackburn MR, Biaggioni I, Carbone DP, Feoktistov I, Dikov MM (2008) Adenosine receptors in regulation of dendritic cell differentiation and function. Blood 112:1822–1831PubMedCrossRefGoogle Scholar
  66. Olsson IL, Breitman TR, Gallo RC (1982) Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3′:5′-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor. Cancer Res 42:3928–3933PubMedGoogle Scholar
  67. Ono K, Akatsu T, Murakami T, Nishikawa M, Yamamoto M, Kugai N, Motoyoshi K, Nagata N (1998) Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2. J Endocrinol 158:R1–R5PubMedCrossRefGoogle Scholar
  68. Ono K, Kaneko H, Choudhary S, Pilbeam CC, Lorenzo JA, Akatsu T, Kugai N, Raisz LG (2005) Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor. J Bone Miner Res 20:23–29PubMedCrossRefGoogle Scholar
  69. Orenstein A, Kachel E, Zuloff-Shani A, Paz Y, Sarig O, Haik J, Smolinsky AK, Mohr R, Shinar E, Danon D (2005) Treatment of deep sternal wound infections post-open heart surgery by application of activated macrophage suspension. Wound Repair Regen 13:237–242PubMedCrossRefGoogle Scholar
  70. Paczesny S, Ueno H, Fay J, Banchereau J, Palucka AK (2003) Dendritic cells as vectors for immunotherapy of cancer. Semin Cancer Biol 13:439–447PubMedCrossRefGoogle Scholar
  71. Park H, Yim M (2007) Rolipram, a phosphodiesterase 4 inhibitor, suppresses PGE2-induced osteoclast formation by lowering osteoclast progenitor cell viability. Arch Pharm Res 30:486–492PubMedCrossRefGoogle Scholar
  72. Park H, Young Lee S, Lee D-S, Yim M (2007) Phosphodiesterase 4 inhibitor regulates the TRANCE/OPG ratio via COX-2 expression in a manner similar to PTH in osteoblasts. Biochem Biophys Res Comm 354:178–183PubMedCrossRefGoogle Scholar
  73. Pastorino S, Massazza S, Cilli M, Varesio L, Bosco MC (2001) Generation of high-titer retroviral vector-producing macrophages as vehicles for in vivo gene transfer. Gene Ther 8:431–441PubMedCrossRefGoogle Scholar
  74. Poppe H, Rybalkin SD, Rehmann H, Hinds TR, Tang X-B, Christensen AE, Schwede F, Genieser H-G, Bos JL, Doskeland SO, Beavo JA, Butt E (2008) Cyclic nucleotide analogs as probes of signaling pathways. Nat Meth 5:277–278CrossRefGoogle Scholar
  75. Ransjö M, Lie A, Mackie EJ (1999) Cholera toxin and forskolin stimulate formation of osteoclast-like cells in mouse marrow cultures and cultured mouse calvarial bones. Eur J Oral Sci 107:45–54PubMedCrossRefGoogle Scholar
  76. Reneland R, Mah S, Kammerer S, Hoyal C, Marnellos G, Wilson S, Sambrook P, Spector T, Nelson M, Braun A (2005) Association between a variation in the phosphodiesterase 4D gene and bone mineral density. BMC Med Genet 6:9PubMedCrossRefGoogle Scholar
  77. Scandella E, Men Y, Gillessen S, Forster R, Groettrup M (2002) Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 100:1354–1361PubMedCrossRefGoogle Scholar
  78. Shayo C, Davio C, Brodsky A, Mladovan AG, Legnazzi BL, Rivera E, Baldi A (1997) Histamine modulates the expression of c-fos through cyclic AMP production via the H2 receptor in the human promonocytic cell line U937. Mol Pharmacol 51:983–990PubMedGoogle Scholar
  79. Shayo C, Fernandez N, Legnazzi BL, Monczor F, Mladovan A, Baldi A, Davio C (2001) Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases. Mol Pharmacol 60:1049–1056PubMedGoogle Scholar
  80. Shayo C, Legnazzi BL, Monczor F, Fernández N, Riveiro ME, Baldi A, Davio C (2004) The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation. Biochem Biophys Res Comm 314:798–804PubMedCrossRefGoogle Scholar
  81. Shepherd MC, Baillie GS, Stirling DI, Houslay MD (2004) Remodelling of the PDE4 cAMP phosphodiesterase isoform profile upon monocyte-macrophage differentiation of human U937 cells. Br J Pharmacol 142:339–351PubMedCrossRefGoogle Scholar
  82. Spina D (2008) PDE4 inhibitors: current status. Br J Pharmacol 155:308–315PubMedCrossRefGoogle Scholar
  83. Takami M, Cho ES, Lee SY, Kamijo R, Yim M (2005) Phosphodiesterase inhibitors stimulate osteoclast formation via TRANCE/RANKL expression in osteoblasts: possible involvement of ERK and p38 MAPK pathways. FEBS Lett 579:832–838PubMedCrossRefGoogle Scholar
  84. Take I, Kobayashi Y, Yamamoto Y, Tsuboi H, Ochi T, Uematsu S, Okafuji N, Kurihara S, Udagawa N, Takahashi N (2005) Prostaglandin E2 strongly inhibits human osteoclast formation. Endocrinology 146:5204–5214PubMedCrossRefGoogle Scholar
  85. Tintut Y, Parhami F, Tsingotjidou A, Tetradis S, Territo M, Demer LL (2002) 8-Isoprostaglandin E2 enhances receptor-activated NFkB ligand (RANKL)-dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP pathway. J Biol Chem 277:14221–14226PubMedCrossRefGoogle Scholar
  86. Torphy TJ, Zhou HL, Cieslinski LB (1992) Stimulation of beta adrenoceptors in a human monocyte cell line (U937) up-regulates cyclic AMP-specific phosphodiesterase activity. J Pharmacol Exp Ther 263:1195–1205PubMedGoogle Scholar
  87. Tortora G, Clair T, Cho-Chung YS (1990) An antisense oligodeoxynucleotide targeted against the type II beta regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects. Proc Natl Acad Sci USA 87:705–708PubMedCrossRefGoogle Scholar
  88. Tortora G, Yokozaki H, Pepe S, Clair T, Cho-Chung YS (1991) Differentiation of HL-60 leukemia by type I regulatory subunit antisense oligodeoxynucleotide of cAMP-dependent protein kinase. Proc Natl Acad Sci USA 88:2011–2015PubMedCrossRefGoogle Scholar
  89. Tudhope SJ, Finney-Hayward TK, Nicholson AG, Mayer RJ, Barnette MS, Barnes PJ, Donnelly LE (2008) Different mitogen-activated protein kinase-dependent cytokine responses in cells of the monocyte lineage. J Pharmacol Exp Ther 324:306–312PubMedCrossRefGoogle Scholar
  90. Vairo G, Argyriou S, Bordun AM, Whitty G, Hamilton JA (1990) Inhibition of the signaling pathways for macrophage proliferation by cyclic AMP. Lack of effect on early responses to colony stimulating factor-1. J Biol Chem 265:2692–2701PubMedGoogle Scholar
  91. Verghese MW, McConnell RT, Lenhard JM, Hamacher L, Jin SL (1995) Regulation of distinct cyclic AMP-specific phosphodiesterase (phosphodiesterase type 4) isozymes in human monocytic cells. Mol Pharmacol 47:1164–1171PubMedGoogle Scholar
  92. Waki Y, Horita T, Miyamoto K-i, Ohya K, Kasugai S (1999) Effects of XT-44, a phosphodiesterase 4 Inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and its therapeutic effects. Jpn J Pharmacol 79:477–483PubMedCrossRefGoogle Scholar
  93. Wani MR, Fuller K, Kim NS, Choi Y, Chambers T (1999) Prostaglandin E2 cooperates with TRANCE in osteoclast induction from hemopoietic precursors: synergistic activation of differentiation, cell spreading, and fusion. Endocrinology 140:1927–1935PubMedCrossRefGoogle Scholar
  94. Wilson NJ, Cross M, Nguyen T, Hamilton JA (2005) cAMP inhibits CSF-1-stimulated tyrosine phosphorylation but augments CSF-1R-mediated macrophage differentiation and ERK activation. FEBS J 272:4141–4152PubMedCrossRefGoogle Scholar
  95. Wilson JM, Ross WG, Agbai ON, Frazier R, Figler RA, Rieger J, Linden J, Ernst PB (2009) The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. J Immunol 182:4616–4623PubMedCrossRefGoogle Scholar
  96. Xaus J, Valledor AF, Cardo M, Marques L, Beleta J, Palacios JM, Celada A (1999) Adenosine inhibits macrophage colony-stimulating factor-dependent proliferation of macrophages through the induction of p27kip-1 expression. J Immunol 163:4140–4149PubMedGoogle Scholar
  97. Yamagami H, Nishioka T, Ochiai E, Fukushima K, Nomura M, Kasugai S, Moritani S, Yokogawa K, Miyamoto K-i (2003) Inhibition of osteoclastogenesis by a phosphodiesterase 4 inhibitor XT-611 through synergistic action with endogenous prostaglandin E2. Biochem Pharmacol 66:801–807PubMedCrossRefGoogle Scholar
  98. Zhu N, Cui J, Qiao C, Li Y, Ma Y, Zhang J, Shen B (2008) cAMP modulates macrophage development by suppressing M-CSF-induced MAPKs activation. Cell Mol Immunol 5:153–157PubMedCrossRefGoogle Scholar
  99. Zuloff-Shani A, Kachel E, Frenkel O, Orenstein A, Shinar E, Danon D (2004) Macrophage suspensions prepared from a blood unit for treatment of refractory human ulcers. Transfus Apher Sci 30:163–167PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Pharmacology, School of MedicineUniversity of WashingtonSeattleUSA

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