Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation

Drug Design, Development and Therapy

Volumn 8, Issue , 2014, Pages 2409-2421

  Srinivasan, Mythily ^a   Blackburn, Corinne ^a   Lahiri, Debomoy K ^b,c  

^a INDIANA UNIVERSITY SCHOOL OF DENTISTRY   (United States)

^b Institute of Psychiatry Research   (United States)

^c INDIANA UNIVERSITY   (United States)

Author keywords

Chronic inflammation; Glucocorticoid induced leucine zipper; Therapeutic potential; Translational impact

Indexed keywords

GLUCOCORTICOID INDUCED LEUCINE ZIPPER PEPTIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN INHIBITOR; SYNAPTOTAGMIN I; UNCLASSIFIED DRUG; PEPTIDE; POLYPROLINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL PROLIFERATION; CELL VIABILITY; CHRONIC INFLAMMATION; CIRCULAR DICHROISM; CONTROLLED STUDY; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME LINKED IMMUNOSORBENT ASSAY; ENZYME RELEASE; HUMAN; HUMAN CELL; IMMUNE RESPONSE; INTERNALIZATION; MACROPHAGE; MOUSE; MULTIPLE SCLEROSIS; MUTAGENESIS; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PROTEIN CONFORMATION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CELL SURVIVAL; CHEMISTRY; CHRONIC DISEASE; DOSE RESPONSE; DRUG EFFECTS; INFLAMMATION; METABOLISM; PATHOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

APOPTOSIS; CELL PROLIFERATION; CELL SURVIVAL; CELLS, CULTURED; CHRONIC DISEASE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INFLAMMATION; MACROPHAGES; NF-KAPPA B; PEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84919336908     PISSN: 11778881     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S59722     Document Type: Article

References (60)

1. Bacher S, Schmitz ML. The NF-kappaB pathway as a potential target for autoimmune disease therapy. Curr Pharm Des. 2004;10(23): 2827–2837.
2. Grilli M, Memo M. Nuclear factor-kappaB/Rel proteins: a point of convergence of signalling pathways relevant in neuronal function and dysfunction. Biochem Pharmacol. 1999;57(1):1–7.
3. Roman-Bias JA, Jimenez SA. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2006;14(9):839–848.
4. Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest. 2001;107(2):135–142.
5. Yan J, Greer JM. NF-kappa B, a potential therapeutic target for the treatment of multiple sclerosis. CNS Neurol Disord Drug Targets. 2008;7(6):536–557.
6. Brown GC, Neher JJ. Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol. 2010;41(2–3): 242–247.
7. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest. 2001;107(1):7–11.
8. Pande V, Ramos MJ. NF-kappaB in human disease: current inhibitors and prospects for de novo structure based design of inhibitors. Curr Med Chem. 2005;12(3):357–374.
9. Lleo A, Galea E, Sastre M. Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases. Cell Mol Life Sci. 2007;64(11):1403–1418.
10. Rao NA, McCalman MT, Moulos P, et al. Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes. Genome Res. 2011;21(9):1404–1416.
11. Potter C, Cordell HJ, Barton A, et al. Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways. Ann Rheum Dis. 2010;69(7): 1315–1320.
12. Fraser JH, Rincon M, McCoy KD, Le Gros G. CTLA4 ligation attenuates AP-1, NFAT and NF-kappaB activity in activated T cells. Eur J Immunol. 1999;29(3):838–844.
13. Fan H, Morand EF. Targeting the side effects of steroid therapy in autoimmune diseases: the role of GILZ. Discov Med. 2012;13(69): 123–133.
14. Cannarile L, Zollo O, D’Adamio F, et al. Cloning, chromosomal assignment and tissue distribution of human GILZ, a glucocorticoid hormone-induced gene. Cell Death Differ. 2001;8(2): 201–203.
15. D’Adamio F, Zollo O, Moraca R, et al. A new dexamethasone-induced gene of the leucine zipper family protects T lymphocytes from TCR/ CD3-activated cell death. Immunity. 1997;7(6):803–812.
16. Ayroldi E, Zollo O, Bastianelli A, et al. GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling. J Clin Invest. 2007;117(6):1605–1615.
17. Berrebi D, Bruscoli S, Cohen N, et al. Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood. 2003;101(2):729–738.
18. Cannarile L, Cuzzocrea S, Santucci L, et al. Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis. Gastroenterology. 2009;136(2):530–541.
19. Cannarile L, Fallarino F, Agostini M, et al. Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines. Blood. 2006;107(3):1039–1047.
20. Di Marco B, Massetti M, Bruscoli S, et al. Glucocorticoid-induced leucine zipper (GILZ)/NF-kappaB interaction: role of GILZ homo-dimerization and C-terminal domain. Nucleic Acids Res. 2007;35(2): 517–528.
21. Ayroldi E, Riccardi C. Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action. FASEB J. 2009;23(11):3649–3658.
22. Riccardi C. GILZ (glucocorticoid-induced leucine zipper), a mediator of the anti-inflammatory and immunosuppressive activity of glucocorticoids. Ann Ig. 2010;22(1 Suppl 1):53–59.
23. Ayroldi E, Migliorati G, Bruscoli S, et al. Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB. Blood. 2001;98(3):743–753.
24. Ball LJ, Kuhne R, Schneider-Mergener J, Oschkinat H. Recognition of proline-rich motifs by protein-protein-interaction domains. Angew Chem Int Ed Engl. 2005;44(19):2852–2869.
25. Ravi Chandra B, Gowthaman R, Raj Akhouri R, Gupta D, Sharma A. Distribution of proline-rich (PxxP) motifs in distinct proteomes: functional and therapeutic implications for malaria and tuberculosis. Protein Eng Des Sel. 2004;17(2):175–182.
26. Srinivasan M, Dunker AK. Proline rich motifs as drug targets in immune mediated disorders. Int J Pept. 2012;2012:634769.
27. Srinivasan M, Janardhanam S. Novel p65 binding glucocorticoid-induced leucine zipper peptide suppresses experimental autoimmune encephalomyelitis. J Biol Chem. 2011;286(52):44799–44810.
28. Srinivasan M, Wardrop RM, Gienapp IE, Stuckman SS, Whitacre CC, Kaumaya PT. A retro-inverso peptide mimic of CD28 encompassing the MYPPPY motif adopts a polyproline type II helix and inhibits encephalitogenic T cells in vitro. J Immunol. 2001;167(1):578–585.
29. Wang MH, Frishman LJ, Otteson DC. Intracellular delivery of proteins into mouse Muller glia cells in vitro and in vivo using Pep-1 transfection reagent. J Neurosci Methods. 2009;177(2):403–419.
30. Klegeris A, Walker DG, McGeer PL. Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells. J Neuroimmunol. 1997;78(1–2):152–161.
31. Lee M, Suk K, Kang Y, McGeer E, McGeer PL. Neurotoxic factors released by stimulated human monocytes and THP-1 cells. Brain Res. 2011;1400:99–111.
32. Harrison LM, Cherla RP, van den Hoogen C, et al. Comparative evaluation of apoptosis induced by Shiga toxin 1 and/or lipopolysaccharides in human monocytic and macrophage-like cells. Microb Pathog. 2005;38(2–3):63–76.
33. Sharif O, Bolshakov VN, Raines S, Newham P, Perkins ND. Transcriptional profiling of the LPS induced NF-kappaB response in macrophages. BMC Immunol. 2007;8:1.
34. Mertlikova-Kaiserova H, Votruba I, Matousova M, Holy A, Hajek M. Role of caspases and CD95/Fas in the apoptotic effects of a nucleotide analog PMEG in CCRF-CEM cells. Anticancer Res. 2010;30(7): 2791–2798.
35. Cen O, Gorska MM, Stafford SJ, Sur S, Alam R. Identification of UNC119 as a novel activator of SRC-type tyrosine kinases. J Biol Chem. 2003;278(10):8837–8845.
36. Srinivasan M, Gienapp IE, Stuckman SS, et al. Suppression of experimental autoimmune encephalomyelitis using peptide mimics of CD28. J Immunol. 2002;169(4):2180–2188.
37. Klegeris A, Walker DG, McGeer PL. Toxicity of human THP-1 monocytic cells towards neuron-like cells is reduced by non-steroidal anti-inflammatory drugs (NSAIDs). Neuropharmacology. 1999;38(7): 1017–1025.
38. Srinivasan M, Janardhanam S. Novel p65 binding glucocorticoid-induced leucine zipper peptide suppresses experimental autoimmune encephalomyelitis. J Biol Chem. 2011;286(52): 44799–44810.
39. Srinivasan R, Rose GD. A physical basis for protein secondary structure. Proc Natl Acad Sci USA. 1999; 96(25):14258–14263.
40. Cubellis MV, Caillez F, Blundell TL, Lovell SC. Properties of polyproline II, a secondary structure element implicated in protein-protein interactions. Proteins. 2005;58(4):880–892.
41. Freund C, Schmalz HG, Sticht J, Kühne R. Proline-rich sequence recognition domain (PRD): ligands, function and inhibition. In: Klussmann E, Scott J, editors. Protein-Protein Interactions as New Drug Targets. Heidelberg, Berlin, Germany: Springer-Verlag; 2008.
42. Gu W, Helms V. Dynamical binding of proline-rich peptides to their recognition domains. Biochim Biophys Acta. 2005;1754(1–2): 232–238.
43. Zarrinpar A, Bhattacharyya RP, Lim WA. The structure and function of proline recognition domains. Sci STKE. 2003;2003(179):RE8.
44. Eguchi M, Kahn M. Design, synthesis, and application of peptide secondary structure mimetics. Mini Rev Med Chem. 2002; 2(5):447–462.
45. Srinivasan M, Roeske RW. Immunomodulatory peptides from IgSF proteins: a review. Curr Protein Pept Sci. 2005;6(2):185–196.
46. Cochran AG. Antagonists of protein-protein interactions. Chem Biol. 2000;7(4):R85–R94.
47. Unal EB, Gursoy A, Erman B. Conformational energies and entropies of peptides, and the peptide-protein binding problem. Phys Biol. 2009;6(3):036014.
48. Groner B, editor. Peptides as Drugs: Discovery and Development. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co KGaA; 2009.
49. Guan QH, Pei DS, Zong YY, Xu TL, Zhang GY Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways. Neuroscience. 2006;139(2):609–627.
50. Mason JM. Design and development of peptides and peptide mimetics as antagonists for therapeutic intervention. Future Med Chem. 2010;2(12):1813–1822.
51. Kurzawa L, Pellerano M, Morris MC. PEP and CADY-mediated delivery of fluorescent peptides and proteins into living cells. Biochim Biophys Acta. 2010;1798(12):2274–2285.
52. Bailey JA, Lahiri DK. A novel effect of rivastigmine on pre-synaptic proteins and neuronal viability in a neurodegeneration model of fetal rat primary cortical cultures and its implication in Alzheimer’s disease. J Neurochem. 2010;112(4):843–853.
53. Bisht S, Khan MA, Bekhit M, et al. A polymeric nanoparticle formulation of curcumin (NanoCurc) ameliorates CC14-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation. Lab Invest. 2011;91(9): 1383–1395.
54. Ray B, Bisht S, Maitra A, Maitra A, Lahiri DK. Neuroprotective and neurorescue effects of a novel polymeric nanoparticle formulation of curcumin (NanoCurc™) in the neuronal cell culture and animal model: implications for Alzheimer’s disease. J Alzheimers Dis. 2011;23(1):61–77.
55. Zhang YH, Mann D, Raymick J, Sarkar S, Paule MG, Lahiri DK, Dumas M, Bell-Cohen A, Schmued LC. Kl 14 inhibits A-beta aggregation and inflammation in vitro and in vivo in AD/Tg mice. Curr Alzheimer Res. 2014;11(3):299–308.
56. Hinkerohe D, Smikalla D, Schoebel A, et al. Dexamethasone prevents LPS-induced microglial activation and astroglial impairment in an experimental bacterial meningitis co-culture model. Brain Res. 2010;1329:45–54.
57. Figuera-Losada M, Rojas C, Slusher BS. Inhibition of microglia activation as a phenotypic assay in early drug discovery. J Biomol Screen. 2014;19(1):17–31.
58. Srinivasan M, Lu D, Eri R, et al. CD80 binding polyproline helical peptide inhibits T cell activation. J Biol Chem. 2005;280(11): 10149–10155.
59. Srinivasan M, Srihari J. Glucocorticoid induced leucine zipper mimic inhibits experimental autoimmune encephalomyelitis. J Immunol. 2012;188 (Meeting Abstract Supplement):Abstract 119.7.
60. Ray B, Lahiri DK. Neuroinflammation in Alzheimer’s disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol. 2009;9(4):434–444.