Proresolution mediators and receptors: Novel drug targets for enhancing pharmacological armamentarium against periodontal inflammation

Infectious Disorders - Drug Targets

Volumn 13, Issue 1, 2013, Pages 75-84

  Grover, Vishakha ^a   Malhotra, Ranjan ^a   Kapoor, Anoop ^b   Singh, Jasvinder ^a   Sachdeva, Sonia ^b  

^a BABA FARID UNIVERSITY OF HEALTH SCIENCES   (India)

^b HIMACHAL PRADESH UNIVERSITY   (India)

Author keywords

Drug targets; Inflammation; Lipid mediator; Lipoxin; Resolution; Resolvin

Indexed keywords

BIOLOGICAL FACTOR; CD59 ANTIGEN; CORTICOTROPIN; CYCLIN DEPENDENT KINASE; CYCLOOXYGENASE 2; DECAY ACCELERATING FACTOR; FORMYLPEPTIDE RECEPTOR; G PROTEIN COUPLED RECEPTOR; HEPOXILIN A; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LEUKOTRIENE B4; LIPOCORTIN 1; LIPOXIN; MARESIN; MITOGEN ACTIVATED PROTEIN KINASE 3; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OMEGA 3 FATTY ACID; PROSTAGLANDIN D2; PROSTAGLANDIN E2; PROSTAGLANDIN J2; RECEPTOR; ROSCOVITINE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CELL INFILTRATION; DRUG TARGETING; GENETIC TRANSCRIPTION; HUMAN; MACROPHAGE; MEDIATOR; NEUTROPHIL; NONHUMAN; PERIODONTITIS; SIGNAL TRANSDUCTION;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIGENS, CD59; DRUG DESIGN; FATTY ACIDS, OMEGA-3; HUMANS; INFLAMMATION MEDIATORS; LEUKOTRIENE ANTAGONISTS; LIPOXINS; MOLECULAR TARGETED THERAPY; PERIODONTITIS; PERIODONTIUM; PROSTAGLANDIN ANTAGONISTS;

EID: 84878754522     PISSN: 18715265     EISSN: 18755852     Source Type: Journal    
DOI: 10.2174/18715265112129990034     Document Type: Article

References (111)

1. Kantarci, A.; Hasturk, H.; Van Dyke, T.E. Host-mediated resolution of inflammation in periodontal diseases, Periodontology, 2000, 2006, 40, 144-163.
2. Serhan, C.N.; Controlling the Resolution of Acute Inflammation: A New Genus of Dual Anti-Inflammatory and Proresolving Mediators. J. Periodontol., 2008, 79, 1520-1526.
3. Hasturk, H.; Kantarci, A.; Surmenian, E.G.; Blackwood, A.; Andry, C.; Serhan, C.N.; Van Dyke, T.E. Resolvin E1 Regulates Inflammation at the Cellular and Tissue Level and Restores Tissue Homeostasis In Vivo. J. Immunol., 2007, 179, 7021-7029.
4. Van Dyke, T.E., The Management of Inflammation in Periodontal Disease, J. Periodontol., 2008, 79, 1601-1608.
5. Hutchinson, J.L.; Rajagopal, S.P.; Sales, K.J.; Jabbour, H.N. Molecular regulators of resolution of inflammation-potential therapeutic targets in the reproductive system, Published online before print April 13, 2011, doi: 10.1530/REP-11-0069
6. Khanna, S.; Biswas, S.; Shang, Y.; Collard, E.; Azad, A. Macrophage Dysfunction Impairs Resolution of Inflammation in the Wounds of Diabetic Mice, 2010 PLoS ONE, 5(3), e9539. doi:10.1371/journal.pone.0009539
7. Ward, S.G. New drug targets in inflammation: efforts to expand the anti-inflammatory armoury, Br. J. Pharmacol., 2008, 153, S5-S6.
8. Serhan, C.N.; Brain, S.D.; Buckley, C.D.; Gilroy, D.W.; Haslett, C.; O'Neill, A.J.; Wallace, J.C. Resolution of inflammation: state of the art, definitions and terms FASEB J., 2007, 21, 325-332.
9. Gilroy, D.W.; Lawrence, T.; Perretti, M.; Rossi, A.G. Inflammatory Resolution: new opportunities for drug discovery, Nat. Rev. Drug Discov., 2004, 3, 401-416.
10. Arita, M.; Bianchini, F.; Aliberti, J.; Sher, A.; Chiang, N.; Hong S. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J. Exp. Med., 2005, 201, 713-722.
11. Arita, M.; Yoshida, M.; Hong, S.; Tjonahen, E.; Glickman, J.N.; Petasis, N.A. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis, Proc. Natl. Acad. Sci. USA, 2005, 102, 7671-7676.
12. Bena, S.; Brancaleone, V.; Wang, J.M.; Perretti, M.; Flower, R.J. Annexin A1 interaction with the FPR2/ALX receptor: identification of distinct domains and downstream associated signaling. J. Biol. Chem., 2012, 287(9), 24690-24697.
13. Arita, M.; Oh, S.F.; Chonan, T.; Hong, S.; Elangovan, S.; Sun, Y.P. Metabolic inactivation of resolvin E1 and stabilization of its antiinflammatory actions, J. Biol. Chem., 2006, 281, 22847-22854.
14. Arita, M.; Ohira, T.; Sun, Y.P.; Elangovan, S.; Chiang, N.; Serhan, C.N. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation, J. Immunol., 2007, 178, 3912-3917.
15. Serhan, C.N.; Chiang, N. Endogenous pro-resolving and antiinflammatory lipid mediators: a new pharmacologic genus, Br. J. Pharmacol., 2008, 153, S200-S215.
16. Serhan, C.N.; Chiang, N.; Van Dyke, T.E. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol., 2008, 8, 349-361.
17. Serhan, C.N.; Clish, C.B.; Brannon, J.; Colgan, S.P.; Chiang, N.; Gronert, K. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med., 2000, 192, 1197-1204.
18. Serhan, C.N.; Hong, S.; Gronert, K.; Colgan, S.P.; Devchand, P.R.; Mirick, G. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med., 2002, 196, 1025-1037.
19. Serhan, C.N.; Jain, A.; Marleau, S.; Clish, C.; Kantarci, A.; Behbehani, B. Reduced inflammation and tissue damage in transgenic rabbits overexpressing 15-lipoxygenase and endogenous antiinflammatory lipid mediators. J. Immunol., 2003, 171, 6856-6865.
20. Serhan, C.N.; Gotlinger, K.; Hong, S.; Arita, M. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat., 2004, 73, 155-172.
21. Serhan, C.N.; Gotlinger, K.; Hong, S.; Lu, Y.; Siegelman, J.; Baer, T. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J. Immunol., 2006, 176, 1848-1859.
22. Serhan, C.N.; Lu, Y.; Hong, S.; Yang, R. Mediator lipidomics: search algorithms for eicosanoids, resolvins, and protectins. Methods Enzymol., 2007, 432, 275-317.
23. Samuelsson, B.; Dahlen, S.E.; Lindgren, J.A.; Rouzer, C.A.; Serhan, C.N. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science, 1987, 237, 1171-1176.
24. Serhan, C.N.; Savill, J. Resolution of inflammation: the beginning programs the end. Nat. Immunol., 2005, 6, 1191-1197.
25. Van Dyke, T.E.; Serhan, C.N. Resolution of Inflammation: A New Paradigm for the Pathogenesis of Periodontal Diseases, JDR., 2003, 82(2), 82-90.
26. Mitchell, S.; Thomas, G.; Harvey, K. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: Stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. J. Am. Soc. Nephrol., 2002, 13, 2497-2507.
27. McMahon, B.; Godson, C. Lipoxins: Endogenous regulators of inflammation. Am. J. Physiol. Renal. Physiol., 2004, 286, F189-F201.
28. Bhatvadekar, N.B.; Williams, R.C. Modulation of the host inflammatory response in periodontal diseases management: exciting new directions, Int. Dent. J., 2009, 59, 305-308.
29. Spite, M.; Serhan, C.N. Novel Lipid Mediators Promote Resolution of Acute Inflammation: Impact of Aspirin and statins. Circ. Res., 2010, 107, 1170-1184.
30. Willoughby, D.A.; Moore, A.R.; Colville-Nash, P.R.; Gilroy, D. Resolution of inflammation. Int. J. Immunopharmacol., 2000, 22, 1131-1135.
31. Cotran, R. S.; Kumar, V.; and Collins, T. Robbins Pathologic Basis of Disease, W.B. Saunders Co.: Philadelphia, Pennsylvania, USA, 1999.
32. Majno, G.; Joris, I. Cells, Tissues, and Disease: Principles of General Pathology: Oxford Univ. Press, New York, New York, USA, 2004.
33. Bannenberg, G.L.; Chiang, N.; Ariel, A.; Arita, M.; Tjonahen, E.; Gotlinger, K.H. Molecular circuits of resolution: formation and actions of resolvins and protectins. J. Immunol., 2005, 174, 4345-4355.
34. Damazo, A. S.; Yona, S.; Flower, R. J.; Perretti, M.; Oliani, S. M.Spatial and temporal profiles for anti-inflammatory gene expression in leukocytes during a resolving model of peritonitis. J. Immunol., 2006, 176, 4410-4418.
35. Serhan, C.N. Special Issue on Lipoxins and Aspirin-Triggered Lipoxins. Prostaglandins Leukot. Essent. Fatty Acids, 2005, 73(34), 139-321.
36. Schwab, J.M.; Chiang, N.; Arita, M.; Serhan, C.N. Resolvin E1 and protectin D1 activa.te inflammation resolution programmes, Nature, 2007, 447, 869-874.
37. Canny, G. Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia. Proc. Natl. Acad. Sci. USA, 2002, 99, 3902-3907.
38. Campbell, E.L. Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution. FASEB J, 2007, 21, 3162-3170.
39. Levy, B.D.; Clish, C.B.; Schmidt, B.; Gronert, K.; Serhan, C.N. Lipid mediator class switching during acute inflammation: signals in resolution. Nature Immunol., 2001, 2, 612-619.
40. Hong, S.; Gronert, K.; Devchand, P.; Moussignac, R.L.; Serhan, C.N. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: autacoids in antiinflammation. J. Biol. Chem., 2003, 278, 14677-14687.
41. Flower, R.J. Prostaglandins, bioassay and inflammation. Br. J. Pharmacol., 2006, 147, S182-S192.
42. Samuelsson, B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science, 1983, 220, 568-575.
43. Serhan, C.N. A search for endogenous mechanisms of antiinflammation uncovers novel chemical mediators: missing links to resolution. Histochem. Cell Biol., 2004, 122, 305-321.
44. WEM. Proceedings of the AOCS Short Course on Polyunsaturated Fatty Acids and Eicosanoids. American Oil Chemists' Society; Champaign, IL, 1987.
45. Van Dyke, T.E.; Serhan, C.N. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J. Dent. Res., 2003, 82, 82-90.
46. Kunkel, S.L.; Ogawa, H.; Conran, P.B.; Ward, P.A.; Zurier, R.B. Suppression of acute and chronic inflammation by orally administered prostaglandins. Arthritis Rheum., 1981, 24, 1151-1158.
47. Hasturk, H. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J. Immunol., 2007, 179, 7021-7029.
48. Williams, T.J.; Jose, P.J.; Wedmore, C.V.; Peck, M.J.; Forrest, M.J. Mechanisms underlying inflammatory edema: the importance of synergism between prostaglandins, leukotrienes, and complementderived peptides. Adv. Prostaglandin Thormboxane Leukot. Res., 1983, 11, 33-37.
49. Pons, F.; Williams, T.J.; Kirk, S.A.; McDonald, F.; Rossi, A.G. Pro-inflammatory and anti-inflammatory effects of the stable prostaglandin D2 analogue, ZK 118.182. Eur. J. Pharmacol., 1994, 261, 237-247.
50. Rajakariar, R. Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxyDelta12 14 PGJ2. Proc. Natl. Acad. Sci. USA, 2007, 104, 20979-20984.
51. Haworth, O.; Buckley, C.D. Resolving the problem of persistence in the switch from acute to chronic inflammation. Proc. Natl. Acad. Sci. USA, 2007, 104, 20647-20648.
52. Van dyke, T.E. Proresolving lipid mediators: potential for prevention and treatment of periodontitis. J. Clin. Periodontol., 2011, 38(11), 119-125.
53. Ariel, A. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution via modulation of CCR5 expression. Nat. Immunol., 2006, 7, 1209-1216.
54. Claria, J.; Serhan, C.N. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc. Natl. Acad. Sci. U S A, 1995, 92, 9475-9479.
55. Chiang, N.; Bermudez, E.A.; Ridker, P.M.; Hurwitz, S.; Serhan, C.N. Aspirin triggers anti-inflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc. Natl. Acad. Sci. USA, 2004, 101, 15178-15183.
56. Claria, J.; Lee, M.H.; Serhan, C.N. Aspirin-triggered lipoxins (15-epi-lx) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol. Med., 1996, 2, 583-596.
57. Morris, T.; Stables, M.; Colville-Nash, P.; Newson, J.; Bellingan, G.; De Souza, P.M.; Gilroy, D.W. Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways. Proc. Natl. Acad. Sci. USA, 2010, 107, 8842-8847.
58. Morris, T.; Stables, M.; Hobbs, A.; De Souza, P.; Colville-Nash, P.; Warner, T.; Newson, J.; Bellingan, G.; Gilroy, D.W. Effects of lowdose aspirin on acute inflammatory responses in humans. J. Immunol., 2009, 183, 2089-2096.
59. Godson, C.; Mitchell, S.; Harvey, K.; Petasis, N.A.; Hogg, N.; Brady, H.R. Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J. Immunol., 2000, 164, 1663-1667.
60. Chiang, N.; Arita, M.; Serhan, C.N. Anti-inflammatory circuitry: lipoxin, aspirin-triggered lipoxins and their receptor ALX. Prostaglandins Leukot. Essent. Fatty Acids, 2005, 73, 163-177.
61. Cash, J.L.; Hart, R.; Russ, A.; Dixon, J.P.; Colledge, W.H.; Doran, J.; Hendrick, A.G.; Carlton, M.B.; Greaves, D.R. Synthetic chemerin-derived peptides suppress inflammation through Chemr23. J. Exp. Med., 2008, 205, 767-775.
62. Roberts, L.J.; Fessel, J.P. The biochemistry of the isoprostane, neuroprostane, and isofuran pathways of lipid peroxidation. Chem. Phys. Lipids., 2004, 128, 173-186.
63. Kohli, P.; Levy, B.D. Resolvins and protectins: mediating solutions to inflammation. Br. J. Pharmacol., 2009, 158, 960-971.
64. Lu, Y.; Hong, S.; Tjonahen, E.; Serhan, C.N. Mediator-lipidomics: databases and search algorithms for PUFA-derived mediators. J. Lipid Res., 2005, 46, 790-802.
65. Sun, Y.P.; Oh, S.F.; Uddin, J.; Yang, R.; Gotlinger, K.; Campbell, E. Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation. J. Biol. Chem., 2007, 282, 9323-9334.
66. Connor, K.M.; SanGiovanni, J.P.; Lofqvist, C.; Aderman, C.M.; Chen, J.; Higuchi, A.; Hong, S.; Pravda, E.A.; Majchrzak, S.; Carper, D.; Hellstrom, A.; Kang, J.X.; Chew, E.Y.; Salem, N. Jr.; Serhan, C.N.; Smith, L.E. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat. Med., 2007, 13, 868-873.
67. Hasturk, H.; Kantarci, A.; Ohira, T.; Arita, M.; Ebrahimi, N.; Chiang, N.; Petasis, N.A.; Levy, B.D.; Serhan, C.N.; Van Dyke, T.E. Rve1 protects from local inflammation and osteoclastmediated bone destruction in periodontitis. FASEB J., 2006, 20, 401-403.
68. Dona, M.; Fredman, G.; Schwab, J.M.; Chiang, N.; Arita, M.; Goodarzi, A.; Cheng, G.; Von Andrian, U.H.; Serhan, C.N. Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood., 2008, 112, 848-855.
69. Ohira, T.; Arita, M.; Omori, K.; Recchiuti, A.; Van Dyke, T.E.; Serhan, C.N. Resolvin E1 receptor activation signals phosphorylation and phagocytosis. J. Biol. Chem., 2010, 285, 3451-3461.
70. Tjonahen, E.; Oh, S.F.; Siegelman, J.; Elangovan, S.; Percarpio, K.B.; Hong, S., Arita, M.; Serhan, C.N. Resolvin E2: identification and anti-inflammatory actions: pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis. Chem Biol., 2006, 13, 1193-1202.
71. Serhan, C.N. Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators. J. Thromb. Haemost., 2009, 7(1), 44-48.
72. Spite, M.; Norling, L.V.; Summers, L.; Yang, R.; Cooper, D.; Petasis, N.A.; Flower, R.J.; Perretti, M.; Serhan, C.N. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature., 2009, 461, 1287-1291.
73. Krishnamoorthy, S.; Recchiuti, A.; Chiang, N.; Yacoubian, S.; Lee, C.H.; Yang, R.; Petasis, N.A.; Serhan, C.N. Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc. Natl. Acad. Sci. USA, 2010, 107, 1660-1665.
74. Serhan, C.N. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu. Rev. Immunol., 2007, 25, 101-137.
75. Mukherjee, P.K.; Marcheselli, V.L.; Serhan, C.N.; Bazan, N.G. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc. Natl. Acad. Sci. USA, 2004, 101, 8491-8496.
76. Levy, B.D.; Kohli, P.; Gotlinger, K.; Haworth, O.; Hong, S.; Kazani, S. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J. Immunol., 2007, 178, 496-502.
77. Duffield, J.S.; Hong, S.; Vaidya, V.S.; Lu, Y.; Fredman, G.; Serhan, C.N. Resolvin D series and protectin D1 mitigate acute kidney injury. J. Immunol., 2006, 177, 5902-5911.
78. Ariel, A.; Li, P.L.; Wang, W.; Tang, W.X.; Fredman, G.; Hong, S.; Gotlinger, K.H.; Serhan, C.N. The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering. J. Biol. Chem., 2005, 280, 43079-43086.
79. Maskrey, B.H.; Megson, I.L.; Whitfield, P.D.; Rossi, A.G. Mechanisms of Resolution of Inflammation A Focus on Cardiovascular Disease. Arterioscler. Thromb. Vasc. Biol., 2011, 31, 1001-1006.
80. Marcheselli, V.L.; Hong, S.; Lukiw, W.J. Novel docosanoids inhibit brain ischemia-reperfusionmediated leukocyte infiltration and proinflammatory gene expression. J. Biol. Chem., 2003, 278, 43807-43817.
81. Gronert, K.; Maheshwari, N.; Khan, N.; Hassan, I.R.; Dunn, M.; Laniado Schwartzman, M. A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J. Biol. Chem., 2005, 280, 15267-15278.
82. Ward, S.G. New drug targets in inflammation: efforts to expand the anti-inflammatory armoury. Br. J. Pharmacol., 2008, 153, S5-S6.
83. Cecil, R.; Pace-Asciak. The hepoxilins and some analogues: a review of their biology. Br. J. Pharmacol., 2009, 158, 972-981.
84. Leitch, A.E.; Haslett, C.; Rossi, A.G. Cyclin-dependent kinase inhibitor drugs as potential novel anti-inflammatory and proresolution agents. Br. J. Pharmacol., 2009, 158, 1004-1016.
85. Vermeulen, K.; Van Bockstaele, D.R.; Berneman, Z.N. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif., 2003, 36, 131-149.
86. Rossi, A.G.; Sawatzky, D.A.; Walker, A.; Ward, C.; Sheldrake, T.A.; Riley, N.A.; Caldicott, A.; Martinez-Losa, M.; Walker, T.R.; Duffin, R.; Gray, M.; Crescenzi, E.; Martin, M.C.; Brady, H.J.; Savill, J.S.; Dransfield, I.; Haslett, C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat. Med., 2006, 12(9), 1056-1064.
87. Duffin, R.; Leitch, A.E.; Sheldrake, T.A.; Hallett, J.M.; Meyer, C.; Fox, S.; Alessandri, A.L.; Martin, M.C.; Brady, H.J.; Teixeira, M.M.; Dransfield, I.; Haslett, C.; Rossi, A.G. The CDK inhibitor, R-roscovitine, promotes eosinophilapoptosis by down-regulation of Mcl-1. FEBS Lett. 2009, 583, 2540-2546.
88. Coussens, L.M.; Werb, Z. Inflammation and cancer. Nature, 2002, 420, 860-867.
89. Hussain, S.P.; Harris, C.C. Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer, 2007, 121, 2373-2380.
90. Edwards, S.W.; Derouet, M.; Howse, M.; Moots, R.J. Regulation of neutrophil apoptosis by Mcl-1. Biochem. Soc. Trans., 2004, 32, 489-492.
91. Dzhagalov, I.; St. John, A.; He, Y.W. The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages. Blood, 2007, 109, 1620-1626.
92. Suzuki, K.; Hino, M.; Hato, F.; Tatsumi, N.; Kitagawa, S. Cytokinespecific activation of distinct mitogen-activated protein kinase subtype cascades in human neutrophils stimulated by granulocyte colony-stimulating factor, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor-alpha. Blood, 1999, 93, 341-349.
93. Ward, C.; Chilvers, E.R.; Lawson, M.F.; Pryde, J.G.; Fujihara, S.; Farrow, S.N. NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro. J. Biol. Chem., 1999, 274, 4309-4318.
94. Lindemans, C.A.; Coffer, P.J. Regulation of granulocyte apoptosis by phosphatidylinositol 3-kinase. Biochem Soc Trans, 2004, 32, 480-484.
95. Meijer, L.; Raymond, E. Roscovitine and other purines as kinase inhibitors. From starfish oocytes to clinical trials. Acc. Chem. Res., 2003, 36, 417-425.
96. Hehl, S.; Stoyanov, B.; Oehrl, W.; Schonherr, R.; Wetzker, R.; Heinemann, S.H. Phosphoinositide 3-kinase-gamma induces Xenopus oocyte maturation via lipid kinase activity. Biochem. J., 2001, 360, 691-698.
97. Yu, C.; Rahmani, M.; Dai, Y.; Conrad, D.; Krystal, G.; Dent, P. The lethal effects of pharmacological cyclin-dependent kinase inhibitors in human leukemia cells proceed through a phosphatidylinositol 3-kinase/Akt-dependent process. Cancer Res., 2003, 63, 1822-1833.
98. Pinho, V.; Souza, D.G.; Barsante, M.M.; Hamer, F.P.; De Freitas, M.S.; Rossi, A.G. Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation. J. Leukoc. Biol., 2005, 77, 800-810.
99. La, M.; D'Amico, M.; Bandiera, S.; Di Filippo, C.; Oliani, S.M.; Gavins, F.N. Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action. FASEB J., 2001, 15, 2247-2256.
100. Hecht, I.; Jiang, R.; Sampaio, A.L.; Hermesh, C.; Rutledge, C.; Shemesh, R. A novel peptide agonist of FPRL1 (ALX) displays anti-inflammatory and cardioprotective effects. J. Pharmacol. Exp. Ther., 2009, 328, 426-434.
101. D'Amico, M.; Di Filippo, C.; La, M.; Solito, E.; McLean, P.G.; Flower, R.J. Lipocortin 1 reduces myocardial ischaemiareperfusion injury by affecting local leukocyte recruitment. FASEB J., 2000, 14, 1867-1869.
102. Perretti, M.; Dalli, J. Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics. Br. J. Pharmacol., 2009, 158, 936-946.
103. Furchgott, R.F.; Zawadzki, J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 1980, 288, 373-376.
104. Palmer, R.M.; Ferrige, A.G. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 1987, 327, 524-526.
105. Moncada, S.; Palmer, R.M. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol. Rev., 1991, 43, 109-142.
106. Quinn, A.C.; Petros, A.J. Nitric oxide: an endogenous gas. Br. J. Anaesth., 1995, 74, 443-451.
107. Kim, Y.M.; Bombeck, C.A. Nitric oxide as a bifunctional regulator of apoptosis. Circ. Res., 1999, 84, 253-256.
108. Taylor, E.L.; Megson, I.L. Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis. Cell Death Differ, 2003, 10, 418-430.
109. Nicotera, P.; Brune, B. Nitric oxide: inducer or suppressor of apoptosis? Trends Pharmacol. Sci., 1997, 18, 189-190.
110. Shaw, C.A.; Taylor, E.L.; Megson, I.L.; Rossi, A.G.; Janeiro, R.D. Nitric oxide and the resolution of inflammation: implications for atherosclerosis, 2005, 100(1), 67-71.
111. Queen Mary University Of London. New-drug-discoverycollaborations-with-queen-mary-university-of-london http://www.mrctechnology.org/news/news_item/(accessed Oct 16, 2012).