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Amino Acids

, Volume 45, Issue 1, pp 41–53 | Cite as

The intriguing mission of neuropeptide Y in the immune system

  • Mirjana DimitrijevićEmail author
  • Stanislava Stanojević
Invited Review

Abstract

For many years, the central nervous system and the immune system were considered two autonomous entities. However, extensive research in the field of neuroimmunomodulation during the past decades has demonstrated the presence of different neuropeptides and their respective receptors in the immune cells. More importantly, it has provided evidence for the direct effects of neuropeptides on the immune cell functions. Neuropeptide Y (NPY) is generally considered the most abundant peptide in the central and peripheral nervous system. However, it is also distinguished by exhibiting pleiotropic functions in many other physiological systems, including the immune system. NPY affects the functions of the cells of the adaptive and innate immunity. In this respect, NPY is known to modulate immune cell trafficking, T helper cell differentiation, cytokine secretion, natural killer cell activity, phagocytosis and the production of reactive oxygen species. The specific Y receptors have been found in immune cells, and their expression is amplified upon immune stimulation. Different Y receptor subtypes may mediate an opposite effect of NPY on the particular function, thus underlining its regulatory role. Since the immune cells are capable of producing NPY upon appropriate stimulation, this peptide can regulate immune cell functions in an autocrine/paracrine manner. NPY also has important implications in several immune-mediated disorders, which affirms the clear need for further investigation of its role in either the mechanisms of the disease development or its possible therapeutic capacity. This review summarises the key points of NPY’s mission throughout the immune system.

Keywords

Neuropeptide Y Y receptors Immune cells Infection Inflammation Autoimmunity 

Notes

Acknowledgments

M. Dimitrijević and S. Stanojević are supported by Grant (175050) from the Ministry of Science, Belgrade, Serbia.

References

  1. Ahmed AA, Wahbi AH, Nordlin K (2001) Neuropeptides modulate a murine monocyte/macrophage cell line capacity for phagocytosis and killing of Leishmania major parasites. Immunopharmacol Immunotoxicol 23:397–409PubMedGoogle Scholar
  2. Baticic L, Detel D, Kucic N, Buljevic S, Pugel EP, Varljen J (2011) Neuroimmunomodulative properties of dipeptidyl peptidase IV/CD26 in a TNBS-induced model of colitis in mice. J Cell Biochem 112:3322–3333PubMedGoogle Scholar
  3. Beck B, Burlet A, Bazin R, Nicolas JP, Burlet C (1993) Elevated neuropeptide Y in the arcuate nucleus of young obese Zucker rats may contribute to the development of their overeating. J Nutr 123:1168–1172PubMedGoogle Scholar
  4. Bedoui S, Kuhlmann S, Nave H, Drube J, Pabst R, von Hörsten S (2001) Differential effects of neuropeptide Y (NPY) on leukocyte subsets in the blood: mobilization of B-1-like B-lymphocytes and activated monocytes. J Neuroimmunol 117:125–132PubMedGoogle Scholar
  5. Bedoui S, Lechner S, Gebhardt T, Nave H, Beck-Sickinger AG, Straub RH, Pabst R, von Hörsten S (2002) NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization. J Neuroimmunol 132:25–33PubMedGoogle Scholar
  6. Bedoui S, Kawamura N, Straub RH, Pabst R, Yamamura T, von Hörsten S (2003a) Relevance of neuropeptide Y for the neuroimmune crosstalk. J Neuroimmunol 134:1–11PubMedGoogle Scholar
  7. Bedoui S, Miyake S, Lin Y, Miyamoto K, Oki S, Kawamura N, Beck-Sickinger A, von Hörsten S, Yamamura T (2003b) Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis: NPY1 receptor-specific inhibition of autoreactive Th1 responses in vivo. J Immunol 171:3451–3458PubMedGoogle Scholar
  8. Bedoui S, Kromer A, Gebhardt T, Jacobs R, Raber K, Dimitrijević M, Heine J, von Hörsten S (2008) Neuropeptide Y receptor-specifically modulates human neutrophil function. J Neuroimmunol 195:88–95PubMedGoogle Scholar
  9. Berglund MM, Hipskind PA, Gehlert DR (2003) Recent developments in our understanding of the physiological role of PP-fold peptide receptor subtypes. Exp Biol Med (Maywood) 228:217–244Google Scholar
  10. Blundell TL, Pitts JE, Tickle IJ, Wood SP, Wu C-W (1981) X-ray analysis (1.4-Å resolution) of avian pancreatic polypeptide: small globular protein hormone. Biochemistry 78:4175–4179Google Scholar
  11. Bracci-Laudiero L, Aloe L, Stenfors C, Tirassa P, Theodorsson E, Lundberg T (1996a) Nerve growth factor stimulates production of neuropeptide Y in human lymphocytes. Neuroreport 7:485–488PubMedGoogle Scholar
  12. Bracci-Laudiero L, Lundeberg T, Stenfors C, Theodorsson E, Tirassa P, Aloe L (1996b) Modification of lymphoid and brain nerve growth factor levels in systemic lupus erythematosus mice. Neurosci Lett 204:13–16PubMedGoogle Scholar
  13. Bracci-Laudiero L, Aloe L, Stenfors C, Theodorsson E, Lundeberg T (1998) Development of systemic lupus erythematosus in mice is associated with alteration of neuropeptide concentrations in inflamed kidneys and immunoregulatory organs. Neurosci Lett 248:97–100PubMedGoogle Scholar
  14. Bradbury AF, Finnie MD, Smyth DG (1982) Mechanism of C-terminal amide formation by pituitary enzymes. Nature 298:686–688PubMedGoogle Scholar
  15. Burton OT, Zaccone P, Phillips JM, De La Peña H, Fehérvári Z, Azuma M, Gibbs S, Stockinger B, Cooke A (2010) Roles for TGF-β and programmed cell death 1 ligand 1 in regulatory T cell expansion and diabetes suppression by zymosan in nonobese diabetic mice. J Immunol 185:2754–2762PubMedGoogle Scholar
  16. Carlson DE, Le W, Chiu WC, Hoffman GE (2009) Messenger RNA for neuropeptide Y in the arcuate nucleus increases in parallel with plasma adrenocorticotropin during sepsis in the rat. Neurosci Lett 452:146–150PubMedGoogle Scholar
  17. Cavadas C, Silva AP, Mosimann F, Cotrim MD, Ribeiro CA, Brunner HR, Grouzmann E (2001) NPY regulates catecholamine secretion from human adrenal chromaffin cells. J Clin Endocrinol Metab 86:5956–5963PubMedGoogle Scholar
  18. Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249PubMedGoogle Scholar
  19. Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640PubMedGoogle Scholar
  20. De la Fuente M, Bernaez I, Del Rio M, Hernanz A (1993) Stimulation of murine peritoneal macrophage functions by neuropeptide Y and peptide YY. Involvement of protein kinase C. Immunology 80:259–265Google Scholar
  21. De la Fuente M, Medina S, Del Rio M, Ferrandez MD, Hernanz A (2000) Effect of aging on the modulation of macrophage functions by neuropeptides. Life Sci 67:2125–2135Google Scholar
  22. De la Fuente M, Del Rio M, Medina S (2001a) Changes with aging in the modulation by neuropeptide Y of murine peritoneal macrophage functions. J Neuroimmunol 116:156–167Google Scholar
  23. De la Fuente M, Del Rio M, Victor VM, Medina S (2001b) Neuropeptide Y effects on murine natural killer activity: changes with ageing and cAMP involvement. Regul Pept 101:73–79Google Scholar
  24. Dimitrijević M, Stanojević S, Vujić V, Beck-Sickinger A, von Hörsten S (2005) Neuropeptide Y and its receptor subtypes specifically modulate rat peritoneal macrophage functions in vitro: counter regulation through Y1 and Y2/5 receptors. Regul Pept 124:163–172PubMedGoogle Scholar
  25. Dimitrijević M, Stanojević S, Mićić S, Vujić V, Kovačević-Jovanović V, Mitić K, von Hörsten S, Kosec D (2006) Neuropeptide Y (NPY) modulates oxidative burst and nitric oxide production in carrageenan-elicited granulocytes from rat air pouch. Peptides 27:3208–3215PubMedGoogle Scholar
  26. Dimitrijević M, Stanojević S, Mitić K, Kuštrimović N, Vujić V, Miletić T, Kovačević-Jovanović V (2008) The anti-inflammatory effect of neuropeptide Y (NPY) in rats is dependent on dipeptidyl peptidase 4 (DP4) activity and age. Peptides 29:2179–2187PubMedGoogle Scholar
  27. Dimitrijević M, Stanojević S, Mitić K, Kuštrimović N, Vujić V, Miletić T, Kovačević-Jovanović V (2010) Modulation of granulocyte functions by peptide YY in the rat: age-related differences in Y receptors expression and plasma dipeptidyl peptidase 4 activity. Regul Pept 159:100–109PubMedGoogle Scholar
  28. Du M, Butchi NB, Woods T, Morgan TW, Peterson KE (2010) Neuropeptide Y has a protective role during murine retrovirus induced neurological disease. J Virol 84:11076–11088PubMedGoogle Scholar
  29. Dyzma M, Boudjeltia KZ, Faraut B, Kerkhofs M (2010) Neuropeptide Y and sleep. Sleep Med Rev 14:161–165PubMedGoogle Scholar
  30. El Karim IA, Lamey PJ, Linden GJ, Lundy FT (2008a) Neuropeptide Y Y1 receptor in human dental pulp cells of noncarious and carious teeth. Int Endod J 41:850–855PubMedGoogle Scholar
  31. El Karim IA, Linden GJ, Orr DF, Lundy FT (2008b) Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites. J Neuroimmunol 200:11–16PubMedGoogle Scholar
  32. Elitsur Y, Luk GD, Colberg M, Gesell MS, Dosescu J, Moshier JA (1994) Neuropeptide Y (NPY) enhances proliferation of human colonic lamina propria lymphocytes. Neuropeptides 26:289–295PubMedGoogle Scholar
  33. Fricker LD (1988) Carboxypeptidase E. Annu Rev Physiol 50:309–321PubMedGoogle Scholar
  34. Friedland JS, Constantin D, Shaw TC, Stylianou E (2001) Regulation of interleukin-8 gene expression after phagocytosis of zymosan by human monocytic cells. J Leukoc Biol 70:447–454PubMedGoogle Scholar
  35. Funkelstein L, Toneff T, Hwang SR, Reinheckel T, Peters C, Hook VYH (2008) Cathepsin L participates in the production of neuropeptide Y in secretory vesicles, demonstrated by protease gene knockout and expression. J Neurochem 106:384–391PubMedGoogle Scholar
  36. Gorrell MD (2005) Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin Sci (Lond) 108:277–292Google Scholar
  37. Groneberg DA, Folkerts G, Peiser C, Chung KF, Fischer A (2004) Neuropeptide Y (NPY). Pulm Pharmacol Ther 17:173–180PubMedGoogle Scholar
  38. Grouzmann E, Comoy E, Bohuon C (1989) Plasma neuropeptide Y concentrations in patients with neuroendocrine tumors. J Clin Endocrinol Metab 68:808–813PubMedGoogle Scholar
  39. Grouzmann E, Fathi M, Gillet M, de Torrente A, Cavadas C, Brunner H, Buclin T (2001) Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma. Clin Chem 47:1075–1082PubMedGoogle Scholar
  40. Han S, Yang CL, Chen X, Naes L, Cox BF, Westfall T (1998) Direct evidence for the role of neuropeptide Y in sympathetic nerve stimulation-induced vasoconstriction. Am J Physiol 274:H290–H294PubMedGoogle Scholar
  41. Harle P, Straub RH, Wiest R, Mayer A, Scholmerich J, Atzeni F, Carrabba M, Cutolo M, Sarzi-Puttini P (2006) Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems. Ann Rheum Dis 65:51–56PubMedGoogle Scholar
  42. Hassani H, Lucas G, Rozell B, Ernfors P (2005) Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling. Am J Physiol Gastrointest Liver Physiol 288:G550–G556PubMedGoogle Scholar
  43. Hayakawa Y, Smyth MJ (2006) CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol 176:1517–1524PubMedGoogle Scholar
  44. Hernanz A, Tato E, De la Fuente M, de Miguel E, Arnalich F (1996) Differential effects of gastrin-releasing peptide, neuropeptide Y, somatostatin and vasoactive intestinal peptide on interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha production by whole blood cells from healthy young and old subjects. J Neuroimmunol 71:25–30PubMedGoogle Scholar
  45. Herzog H, Hort YJ, Ball HJ, Hayes G, Shine J, Selbie LA (1992) Cloned human neuropeptide Y receptor couples to two different second messenger systems. Proc Natl Acad Sci USA 89:5794–5798PubMedGoogle Scholar
  46. Higuchi H, Yang H-YT, Sabol SL (1988) Rat neuropeptide Y precursor gene expression. mRNA structure, tissue distribution, and regulation by glucocorticoids, cyclic AMP, and phorbol ester. J Biol Chem 263:6288–6295PubMedGoogle Scholar
  47. Hill JW, Elmquist JK, Elias CF (2008) Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab 294:E827–E832PubMedGoogle Scholar
  48. Hirai H, Miura J, Hu Y, Larsson H, Larsson K, Lernmark A, Ivarsson SA, Wu T, Kingman A, Tzioufas AG, Notkins AL (2008) Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens. Clin Immunol 127:366–374PubMedGoogle Scholar
  49. Holler J, Zakrzewicz A, Kaufmann A, Wilhelm J, Fuchs-Moll G, Dietrich H, Padberg W, Kuncova J, Kummer W, Grau V (2008) Neuropeptide Y is expressed by rat mononuclear blood leukocytes and strongly down-regulated during inflammation. J Immunol 181:6906–6912PubMedGoogle Scholar
  50. Irwin M, Hauger R, Brown M (1992) Central corticotropin-releasing hormone activates the sympathetic nervous system and reduces immune function: increased responsivity of the aged rat. Endocrinology 131:1047–1053PubMedGoogle Scholar
  51. Jacob HJ, Pettersson A, Wilson D, Mao Y, Lernmark A, Lander ES (1992) Genetic dissection of autoimmune type I diabetes in the BB rat. Nat Genet 2:56–60PubMedGoogle Scholar
  52. Kawamura N, Tamura H, Obana S, Wenner M, Ishikawa T, Nakata A, Yamamoto H (1998) Differential effects of neuropeptides on cytokine production by mouse helper T cell subsets. Neuroimmunomodulation 5:9–15PubMedGoogle Scholar
  53. Kim YW, Kim KH, Ahn DK, Kim HS, Kim JY, Lee DC, Park SY (2007) Time-course changes of hormones and cytokines by lipopolysaccharide and its relation with anorexia. J Physiol Sci 57:159–165PubMedGoogle Scholar
  54. Klompus M, Ho W, Sharkey KA, McKay DM (2010) Antisecretory effects of neuropeptide Y in the mouse colon are region-specific and are lost in DSS-induced colitis. Regul Pept 165:138–145PubMedGoogle Scholar
  55. Kobzik L (1995) Lung macrophage uptake of unopsonized environmental particulates. Role of scavenger-type receptors. J Immunol 155:367–376PubMedGoogle Scholar
  56. Lambert RW, Campton K, Ding W, Ozawa H, Granstein RD (2002) Langerhans cell expression of neuropeptide Y and peptide YY. Neuropeptides 36:246–251PubMedGoogle Scholar
  57. Larhammar D, Wraith A, Berglund MM, Holmberg SK, Lundell I (2001) Origins of the many NPY-family receptors in mammals. Peptides 22:295–307PubMedGoogle Scholar
  58. Levite M (1998) Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. Proc Natl Acad Sci USA 95:12544–12549PubMedGoogle Scholar
  59. Levite M (2000) Nerve-driven immunity. The direct effects of neurotransmitters on T-cell function. Ann NY Acad Sci 917:307–321PubMedGoogle Scholar
  60. Levite M, Cahalon L, Hershkoviz R, Steinman L, Lider O (1998) Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin. J Immunol 160:993–1000PubMedGoogle Scholar
  61. Liu J, Li J, Zhai N, Geng L, Song F (2004) Detection of the levels of neuropeptides, ACTH and cortisol in the blood of patients with polymyositis/dermatomyositis and their significance. J Dermatol 31:392–397PubMedGoogle Scholar
  62. Lundberg JM, Terenius L, Hokfelt T, Goldstein M (1983) High levels of neuropeptide Y in peripheral noradrenergic neurons in various mammals including man. Neurosci Lett 42:167–172PubMedGoogle Scholar
  63. Lundberg JM, Saria A, Franco-Cereceda A, Hokfelt T, Terenius L, Goldstein M (1985) Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons. Naunyn Schmiedebergs Arch Pharmacol 328:331–340PubMedGoogle Scholar
  64. Maeda K, Yasuda M, Kaneda H, Maeda S, Yamadori A (1994) Cerebrospinal fluid (CSF) neuropeptide Y- and somatostatin-like immunoreactivities in man. Neuropeptides 27:323–332PubMedGoogle Scholar
  65. Malessa R, Heimbach M, Brockmeyer NH, Hengge U, Rascher W, Michel MC (1996) Increased neuropeptide Y-like immunoreactivity in cerebrospinal fluid and plasma of human immunodeficiency virus-infected patients: relationship to HIV encephalopathy. J Neurol Sci 136:154–158PubMedGoogle Scholar
  66. Medina S, Rio MD, Cuadra BD, Guayerbas N, Fuente MD (1999) Age-related changes in the modulatory action of gastrin-releasing peptide, neuropeptide Y and sulfated cholecystokinin octapeptide in the proliferation of murine lymphocytes. Neuropeptides 33:173–179PubMedGoogle Scholar
  67. Medina S, Del Rio M, Hernanz A, De la Fuente M (2000a) Age-related changes in the neuropeptide Y effects on murine lymphoproliferation and interleukin-2 production. Peptides 21:1403–1409PubMedGoogle Scholar
  68. Medina S, Del Rio M, Hernanz A, De la Fuente M (2000b) The NPY effects on murine leukocyte adherence and chemotaxis change with age. Adherent cell implication. Regul Pept 95:35–45PubMedGoogle Scholar
  69. Meltzer JC, Grimm PC, Greenberg AH, Nance DM (1997) Enhanced immunohistochemical detection of autonomic nerve fibers, cytokines and inducible nitric oxide synthase by light and fluorescent microscopy in rat spleen. J Histochem Cytochem 45:599–610PubMedGoogle Scholar
  70. Mentlein R (1999) Dipeptidyl-peptidase IV (CD26)—role in the inactivation of regulatory peptides. Regul Pept 85:9–24PubMedGoogle Scholar
  71. Mentlein R, Roos T (1996) Proteases involved in the metabolism of angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), and neuropeptide Y by vascular smooth muscle cells. Peptides 17:709–720PubMedGoogle Scholar
  72. Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T (1998) XVI International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev 50:143–150PubMedGoogle Scholar
  73. Mitić K, Stanojević S, Kuštrimović N, Vujić V, Dimitrijević M (2011) Neuropeptide Y modulates functions of inflammatory cells in the rat: distinct role for Y1, Y2 and Y5 receptors. Peptides 32:1626–1633PubMedGoogle Scholar
  74. Morales-Medina JC, Dumont Y, Quirion R (2010) A possible role of neuropeptide Y in depression and stress. Brain Res 1314:194–205PubMedGoogle Scholar
  75. Muller S, Weihe E (1991) Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus. Brain Behav Immun 5:55–72PubMedGoogle Scholar
  76. Mullins DE, Zhang X, Hawes BE (2002) Activation of extracellular signal regulated protein kinase by neuropeptide Y and pancreatic polypeptide in CHO cells expressing the NPY Y(1), Y(2), Y(4) and Y(5) receptor subtypes. Regul Pept 105:65–73PubMedGoogle Scholar
  77. Myers AK, Farhat MY, Vaz CA, Keiser HR, Zukowska-Grojec Z (1988) Release of immunoreactive-neuropeptide by rat platelets. Biochem Biophys Res Commun 155:118–122PubMedGoogle Scholar
  78. Nair MP, Schwartz SA, Wu K, Kronfol Z (1993) Effect of neuropeptide Y on natural killer activity of normal human lymphocytes. Brain Behav Immun 7:70–78PubMedGoogle Scholar
  79. Nave H, Bedoui S, Moenter F, Steffens J, Felies M, Gebhardt T, Straub RH, Pabst R, Dimitrijević M, Stanojević S, von Hörsten S (2004) Reduced tissue immigration of monocytes by neuropeptide Y during endotoxemia is associated with Y2 receptor activation. J Neuroimmunol 155:1–12PubMedGoogle Scholar
  80. Nishizuka Y (1984) The role of protein kinase-C in cell surface signal transduction and tumor promotion. Nature 308:693–697PubMedGoogle Scholar
  81. Nohr D, Weihe E (1991) The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers. Brain Behav Immun 5:84–101PubMedGoogle Scholar
  82. Pandey SC, Zhang H, Roy A, Xu T (2005) Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest 115:2762–2773PubMedGoogle Scholar
  83. Pang XH, Li TK, Xie Q, He FQ, de Cui J, Chen YQ, Huang XL, Gan HT (2010) Amelioration of dextran sulfate sodium-induced colitis by neuropeptide Y antisense oligodeoxynucleotide. Int J Colorectal Dis 25:1047–1053PubMedGoogle Scholar
  84. Pereira da Silva JA, Carmo-Fonseca M (1990) Peptide containing nerves in human synovium: immunohistochemical evidence for decreased innervation in rheumatoid arthritis. J Rheumatol 17:1592–1599PubMedGoogle Scholar
  85. Petitto JM, Huang Z, McCarthy DB (1994) Molecular cloning of NPY-Y1 receptor cDNA from rat splenic lymphocytes: evidence of low levels of mRNA expression and [125I]NPY binding sites. J Neuroimmunol 54:81–86PubMedGoogle Scholar
  86. Puerto M, Guayerbas N, Alvarez P, De la Fuente M (2005) Modulation of neuropeptide Y and norepinephrine on several leucocyte functions in adult, old and very old mice. J Neuroimmunol 165:33–40PubMedGoogle Scholar
  87. Reich A, Orda A, Wisnicka B, Szepietowski JC (2007) Plasma concentration of selected neuropeptides in patients suffering from psoriasis. Exp Dermatol 16:421–428PubMedGoogle Scholar
  88. Reinhold D, Kahne T, Steinbrecher A, Wrenger S, Neubert K, Ansorge S, Brocke S (2002) The role of dipeptidyl peptidase IV (DP IV) enzymatic activity in T cell activation and autoimmunity. Biol Chem 383:1133–1138PubMedGoogle Scholar
  89. Rethnam S, Raju B, Fristad I, Berggreen E, Heyeraas KJ (2010) Differential expression of neuropeptide Y Y1 receptors during pulpal inflammation. Int Endod J 43:492–498PubMedGoogle Scholar
  90. Romano TA, Felten SY, Felten DL, Olschowka JA (1991) Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide. Brain Behav Immun 5:116–131PubMedGoogle Scholar
  91. Salomon J, Baran E (2008) The role of selected neuropeptides in pathogenesis of atopic dermatitis. J Eur Acad Dermatol Venereol 22:223–228PubMedGoogle Scholar
  92. Santavirta N, Konttinen YT, Törnwall J, Segerberg M, Santavirta S, Matucci-Cerinic M, Björvell H (1997) Neuropeptides of the autonomic nervous system in Sjogren’s syndrome. Ann Rheum Dis 56:737–740PubMedGoogle Scholar
  93. Saurer TB, Ijames SG, Lysle DT (2006) Neuropeptide Y Y1 receptors mediate morphine-induced reductions of natural killer cell activity. J Neuroimmunol 177:18–26PubMedGoogle Scholar
  94. Schwarz H, Villiger PM, von Kempis J, Lotz M (1994) Neuropeptide Y is an inducible gene in the human immune system. J Neuroimmunol 51:53–61PubMedGoogle Scholar
  95. Shibata M, Hisajima T, Nakano M, Goris RC, Funakoshi K (2008) Morphological relationships between peptidergic nerve fibers and immunoglobulin A-producing lymphocytes in the mouse intestine. Brain Behav Immun 22:158–166PubMedGoogle Scholar
  96. Shimizu M, Shigeri Y, Tatsu Y, Yoshikawa S, Yumoto N (1998) Enhancement of antimicrobial activity of neuropeptide Y by N-terminal truncation. Antimicrob Agents Chemother 42:2745–2746PubMedGoogle Scholar
  97. Simpson KA, Martin NM, Bloom SR (2009) Hypothalamic regulation of food intake and clinical therapeutic applications. Arq Bras Endocrinol Metab 53:120–128Google Scholar
  98. Sipos G, Altdorfer K, Pongor E, Chen LP, Feher E (2006) Neuroimmune link in the mucosa of chronic gastritis with Helicobacter pylori infection. Dig Dis Sci 51:1810–1817PubMedGoogle Scholar
  99. Soder O, Hellstrom PM (1987) Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. Int Arch Allergy Appl Immunol 84:205–211PubMedGoogle Scholar
  100. Souli A, Chariot J, Voisin T, Presset O, Tsocas A, Balasubramaniam A, Laburthe M, Roze C (1997) Several receptors mediate the antisecretory effect of peptide YY, neuropeptide Y, and pancreatic polypeptide on VIP-induced fluid secretion in the rat jejunum in vivo. Peptides 18:551–557PubMedGoogle Scholar
  101. Stanojević S, Vujić V, Kovačević-Jovanović V, Mitić K, Kosec D, Hörsten S, Dimitrijević M (2006) Age-related effect of peptide YY (PYY) on paw edema in the rat: the function of Y1 receptors on inflammatory cells. Exp Gerontol 41:793–799PubMedGoogle Scholar
  102. Stanojević S, Mitić K, Vujić V, Kovačević-Jovanović V, Dimitrijević M (2007) Exposure to acute physical and psychological stress alters the response of rat macrophages to corticosterone, neuropeptide Y and beta-endorphin. Stress 10:65–73PubMedGoogle Scholar
  103. Steinbrecher A, Reinhold D, Quigley L, Gado A, Tresser N, Izikson L, Born I, Faust J, Neubert K, Martin R, Ansorge S, Brocke S (2001) Targeting dipeptidyl peptidase IV (CD26) suppresses autoimmune encephalomyelitis and up-regulates TGF-beta 1 secretion in vivo. J Immunol 166:2041–2048PubMedGoogle Scholar
  104. Stevens-Felten SY, Bellinger DL (1997) Noradrenergic and peptidergic innervation of lymphoid organs. Chem Immunol 69:99–131PubMedGoogle Scholar
  105. Straub RH, Mayer M, Kreutz M, Leeb S, Scholmerich J, Falk W (2000) Neurotransmitters of the sympathetic nerve terminal are powerful chemoattractants for monocytes. J Leukoc Biol 67:553–558PubMedGoogle Scholar
  106. Talme T, Liu Z, Sundqvist KG (2008) The neuropeptide calcitonin gene-related peptide (CGRP) stimulates T cell migration into collagen matrices. J Neuroimmunol 196:60–66PubMedGoogle Scholar
  107. Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296:659–660PubMedGoogle Scholar
  108. Thompson AC, Justice JB Jr, McDonald JK (1995) Quantitative microdialysis of neuropeptide Y. J Neurosci Methods 60:189–198PubMedGoogle Scholar
  109. Unitt J, Hornigold D (2011) Plant lectins are novel Toll-like receptor agonists. Biochem Pharmacol 81:1324–1328PubMedGoogle Scholar
  110. Vouldoukis I, Shai Y, Nicolas P, Mor A (1996) Broad spectrum antibiotic activity of the skin-PYY. FEBS Lett 380:237–240PubMedGoogle Scholar
  111. Watson JD, Sury MR, Corder R, Carson R, Bouloux PM, Lowry PJ, Besser GM, Hinds CJ (1988) Plasma levels of neuropeptide tyrosine Y (NPY) are increased in human sepsis but are unchanged during canine endotoxin shock despite raised catecholamine concentrations. J Endocrinol 116:421–426PubMedGoogle Scholar
  112. Weihe E, Bette M, Preuss MA, Faber M, Schäfer MK, Rehnelt J, Schnell MJ, Dietzschold B (2008) Role of virus-induced neuropeptides in the brain in the pathogenesis of rabies. Dev Biol (Basel) 131:73–81Google Scholar
  113. Wheway J, Mackay CR, Newton RA, Sainsbury A, Boey D, Herzog H, Mackay F (2005) A fundamental bimodal role for neuropeptide Y1 receptor in the immune system. J Exp Med 202:1527–1538PubMedGoogle Scholar
  114. Wheway J, Herzog H, Mackay F (2007) The Y1 receptor for NPY: a key modulator of the adaptive immune system. Peptides 28:453–458PubMedGoogle Scholar
  115. Wiest R, Moleda L, Zietz B, Hellerbrand C, Schölmerich J, Straub R (2008) Uncoupling of sympathetic nervous system and hypothalamic-pituitary–adrenal axis in cirrhosis. J Gastroenterol Hepatol 23:1901–1908PubMedGoogle Scholar
  116. Xapelli S, Agasse F, Ferreira R, Silva AP, Malva JO (2006) Neuropeptide Y as an endogenous antiepileptic, neuroprotective and pro-neurogenic peptide. Recent Pat CNS Drug Discov 1:315–324PubMedGoogle Scholar
  117. Zhou JR, Xu Z, Jiang CL (2008) Neuropeptide Y promotes TGF-beta1 production in RAW264.7 cells by activating PI3K pathway via Y1 receptor. Neurosci Bull 24:155–159PubMedGoogle Scholar
  118. Zukowska-Grojec Z, Vaz AC (1988) Role of neuropeptide Y (NPY) in cardiovascular responses to stress. Synapse 2:293–298PubMedGoogle Scholar
  119. Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Rose W, Rone J, Movafagh S, Ji H, Yeh Y, Chen WT, Kleinman HK, Grouzmann E, Grant DS (1998) Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circ Res 83:187–195PubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Institute of Virology, Vaccines and Sera, “Torlak”, Immunology Research Center “Branislav Janković”BelgradeSerbia

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