Skip to main content

Advertisement

SpringerLink
Log in

The intriguing mission of neuropeptide Y in the immune system

  • Invited Review
  • Published:
Amino Acids Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • 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 23:397–409

    CAS  PubMed  Google Scholar 

  • 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 112:3322–3333

    CAS  PubMed  Google Scholar 

  • 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 123:1168–1172

    CAS  PubMed  Google Scholar 

  • 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 117:125–132

    CAS  PubMed  Google Scholar 

  • 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 132:25–33

    CAS  PubMed  Google Scholar 

  • Bedoui S, Kawamura N, Straub RH, Pabst R, Yamamura T, von Hörsten S (2003a) Relevance of neuropeptide Y for the neuroimmune crosstalk. J Neuroimmunol 134:1–11

    CAS  PubMed  Google Scholar 

  • 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 171:3451–3458

    CAS  PubMed  Google Scholar 

  • 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 195:88–95

    CAS  PubMed  Google Scholar 

  • 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) 228:217–244

    CAS  Google Scholar 

  • 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 78:4175–4179

    CAS  Google Scholar 

  • 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 7:485–488

    CAS  PubMed  Google Scholar 

  • 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 204:13–16

    CAS  PubMed  Google Scholar 

  • 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 248:97–100

    CAS  PubMed  Google Scholar 

  • Bradbury AF, Finnie MD, Smyth DG (1982) Mechanism of C-terminal amide formation by pituitary enzymes. Nature 298:686–688

    CAS  PubMed  Google Scholar 

  • 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 185:2754–2762

    CAS  PubMed  Google Scholar 

  • 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 452:146–150

    CAS  PubMed  Google Scholar 

  • 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 86:5956–5963

    CAS  PubMed  Google Scholar 

  • Cooper HS, Murthy SN, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249

    CAS  PubMed  Google Scholar 

  • Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640

    CAS  PubMed  Google Scholar 

  • 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 80:259–265

    Google Scholar 

  • 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 67:2125–2135

    Google Scholar 

  • 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 116:156–167

    Google Scholar 

  • 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 101:73–79

    Google Scholar 

  • 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 124:163–172

    PubMed  Google Scholar 

  • 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 27:3208–3215

    PubMed  Google Scholar 

  • 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 29:2179–2187

    PubMed  Google Scholar 

  • 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 159:100–109

    PubMed  Google Scholar 

  • 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 84:11076–11088

    CAS  PubMed  Google Scholar 

  • Dyzma M, Boudjeltia KZ, Faraut B, Kerkhofs M (2010) Neuropeptide Y and sleep. Sleep Med Rev 14:161–165

    PubMed  Google Scholar 

  • 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 41:850–855

    CAS  PubMed  Google Scholar 

  • 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 200:11–16

    CAS  PubMed  Google Scholar 

  • 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 26:289–295

    CAS  PubMed  Google Scholar 

  • Fricker LD (1988) Carboxypeptidase E. Annu Rev Physiol 50:309–321

    CAS  PubMed  Google Scholar 

  • 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 70:447–454

    CAS  PubMed  Google Scholar 

  • 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 106:384–391

    CAS  PubMed  Google Scholar 

  • Gorrell MD (2005) Dipeptidyl peptidase IV and related enzymes in cell biology and liver disorders. Clin Sci (Lond) 108:277–292

    CAS  Google Scholar 

  • Groneberg DA, Folkerts G, Peiser C, Chung KF, Fischer A (2004) Neuropeptide Y (NPY). Pulm Pharmacol Ther 17:173–180

    CAS  PubMed  Google Scholar 

  • Grouzmann E, Comoy E, Bohuon C (1989) Plasma neuropeptide Y concentrations in patients with neuroendocrine tumors. J Clin Endocrinol Metab 68:808–813

    CAS  PubMed  Google Scholar 

  • 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 47:1075–1082

    CAS  PubMed  Google Scholar 

  • 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–H294

    CAS  PubMed  Google Scholar 

  • 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 65:51–56

    CAS  PubMed  Google Scholar 

  • 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–G556

    CAS  PubMed  Google Scholar 

  • Hayakawa Y, Smyth MJ (2006) CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol 176:1517–1524

    CAS  PubMed  Google Scholar 

  • 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 71:25–30

    CAS  PubMed  Google Scholar 

  • 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 89:5794–5798

    CAS  PubMed  Google Scholar 

  • 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 263:6288–6295

    CAS  PubMed  Google Scholar 

  • Hill JW, Elmquist JK, Elias CF (2008) Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab 294:E827–E832

    CAS  PubMed  Google Scholar 

  • 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 127:366–374

    CAS  PubMed  Google Scholar 

  • 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 181:6906–6912

    CAS  PubMed  Google Scholar 

  • 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 131:1047–1053

    CAS  PubMed  Google Scholar 

  • 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 2:56–60

    CAS  PubMed  Google Scholar 

  • 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 5:9–15

    CAS  PubMed  Google Scholar 

  • 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 57:159–165

    PubMed  Google Scholar 

  • 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 165:138–145

    CAS  PubMed  Google Scholar 

  • Kobzik L (1995) Lung macrophage uptake of unopsonized environmental particulates. Role of scavenger-type receptors. J Immunol 155:367–376

    CAS  PubMed  Google Scholar 

  • Lambert RW, Campton K, Ding W, Ozawa H, Granstein RD (2002) Langerhans cell expression of neuropeptide Y and peptide YY. Neuropeptides 36:246–251

    CAS  PubMed  Google Scholar 

  • Larhammar D, Wraith A, Berglund MM, Holmberg SK, Lundell I (2001) Origins of the many NPY-family receptors in mammals. Peptides 22:295–307

    CAS  PubMed  Google Scholar 

  • 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 95:12544–12549

    CAS  PubMed  Google Scholar 

  • Levite M (2000) Nerve-driven immunity. The direct effects of neurotransmitters on T-cell function. Ann NY Acad Sci 917:307–321

    CAS  PubMed  Google Scholar 

  • Levite M, Cahalon L, Hershkoviz R, Steinman L, Lider O (1998) Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin. J Immunol 160:993–1000

    CAS  PubMed  Google Scholar 

  • 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 31:392–397

    CAS  PubMed  Google Scholar 

  • 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 42:167–172

    CAS  PubMed  Google Scholar 

  • 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 328:331–340

    CAS  PubMed  Google Scholar 

  • Maeda K, Yasuda M, Kaneda H, Maeda S, Yamadori A (1994) Cerebrospinal fluid (CSF) neuropeptide Y- and somatostatin-like immunoreactivities in man. Neuropeptides 27:323–332

    CAS  PubMed  Google Scholar 

  • 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 136:154–158

    CAS  PubMed  Google Scholar 

  • 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 33:173–179

    CAS  PubMed  Google Scholar 

  • 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 21:1403–1409

    CAS  PubMed  Google Scholar 

  • 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 95:35–45

    CAS  PubMed  Google Scholar 

  • 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 45:599–610

    CAS  PubMed  Google Scholar 

  • Mentlein R (1999) Dipeptidyl-peptidase IV (CD26)—role in the inactivation of regulatory peptides. Regul Pept 85:9–24

    CAS  PubMed  Google Scholar 

  • 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 17:709–720

    CAS  PubMed  Google Scholar 

  • 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 50:143–150

    CAS  PubMed  Google Scholar 

  • 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 32:1626–1633

    PubMed  Google Scholar 

  • Morales-Medina JC, Dumont Y, Quirion R (2010) A possible role of neuropeptide Y in depression and stress. Brain Res 1314:194–205

    CAS  PubMed  Google Scholar 

  • Muller S, Weihe E (1991) Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus. Brain Behav Immun 5:55–72

    CAS  PubMed  Google Scholar 

  • 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 105:65–73

    CAS  PubMed  Google Scholar 

  • Myers AK, Farhat MY, Vaz CA, Keiser HR, Zukowska-Grojec Z (1988) Release of immunoreactive-neuropeptide by rat platelets. Biochem Biophys Res Commun 155:118–122

    CAS  PubMed  Google Scholar 

  • Nair MP, Schwartz SA, Wu K, Kronfol Z (1993) Effect of neuropeptide Y on natural killer activity of normal human lymphocytes. Brain Behav Immun 7:70–78

    CAS  PubMed  Google Scholar 

  • 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 155:1–12

    CAS  PubMed  Google Scholar 

  • Nishizuka Y (1984) The role of protein kinase-C in cell surface signal transduction and tumor promotion. Nature 308:693–697

    CAS  PubMed  Google Scholar 

  • 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 5:84–101

    CAS  PubMed  Google Scholar 

  • 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 115:2762–2773

    CAS  PubMed  Google Scholar 

  • 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 25:1047–1053

    PubMed  Google Scholar 

  • Pereira da Silva JA, Carmo-Fonseca M (1990) Peptide containing nerves in human synovium: immunohistochemical evidence for decreased innervation in rheumatoid arthritis. J Rheumatol 17:1592–1599

    CAS  PubMed  Google Scholar 

  • 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 54:81–86

    CAS  PubMed  Google Scholar 

  • 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 165:33–40

    CAS  PubMed  Google Scholar 

  • Reich A, Orda A, Wisnicka B, Szepietowski JC (2007) Plasma concentration of selected neuropeptides in patients suffering from psoriasis. Exp Dermatol 16:421–428

    CAS  PubMed  Google Scholar 

  • 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 383:1133–1138

    CAS  PubMed  Google Scholar 

  • Rethnam S, Raju B, Fristad I, Berggreen E, Heyeraas KJ (2010) Differential expression of neuropeptide Y Y1 receptors during pulpal inflammation. Int Endod J 43:492–498

    CAS  PubMed  Google Scholar 

  • Romano TA, Felten SY, Felten DL, Olschowka JA (1991) Neuropeptide-Y innervation of the rat spleen: another potential immunomodulatory neuropeptide. Brain Behav Immun 5:116–131

    CAS  PubMed  Google Scholar 

  • Salomon J, Baran E (2008) The role of selected neuropeptides in pathogenesis of atopic dermatitis. J Eur Acad Dermatol Venereol 22:223–228

    CAS  PubMed  Google Scholar 

  • 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 56:737–740

    CAS  PubMed  Google Scholar 

  • Saurer TB, Ijames SG, Lysle DT (2006) Neuropeptide Y Y1 receptors mediate morphine-induced reductions of natural killer cell activity. J Neuroimmunol 177:18–26

    CAS  PubMed  Google Scholar 

  • Schwarz H, Villiger PM, von Kempis J, Lotz M (1994) Neuropeptide Y is an inducible gene in the human immune system. J Neuroimmunol 51:53–61

    CAS  PubMed  Google Scholar 

  • 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 22:158–166

    CAS  PubMed  Google Scholar 

  • 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 42:2745–2746

    CAS  PubMed  Google Scholar 

  • Simpson KA, Martin NM, Bloom SR (2009) Hypothalamic regulation of food intake and clinical therapeutic applications. Arq Bras Endocrinol Metab 53:120–128

    Google Scholar 

  • 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 51:1810–1817

    CAS  PubMed  Google Scholar 

  • Soder O, Hellstrom PM (1987) Neuropeptide regulation of human thymocyte, guinea pig T lymphocyte and rat B lymphocyte mitogenesis. Int Arch Allergy Appl Immunol 84:205–211

    CAS  PubMed  Google Scholar 

  • 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 18:551–557

    CAS  PubMed  Google Scholar 

  • 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 41:793–799

    PubMed  Google Scholar 

  • 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 10:65–73

    PubMed  Google Scholar 

  • 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 166:2041–2048

    CAS  PubMed  Google Scholar 

  • Stevens-Felten SY, Bellinger DL (1997) Noradrenergic and peptidergic innervation of lymphoid organs. Chem Immunol 69:99–131

    CAS  PubMed  Google Scholar 

  • 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 67:553–558

    CAS  PubMed  Google Scholar 

  • Talme T, Liu Z, Sundqvist KG (2008) The neuropeptide calcitonin gene-related peptide (CGRP) stimulates T cell migration into collagen matrices. J Neuroimmunol 196:60–66

    CAS  PubMed  Google Scholar 

  • Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296:659–660

    CAS  PubMed  Google Scholar 

  • Thompson AC, Justice JB Jr, McDonald JK (1995) Quantitative microdialysis of neuropeptide Y. J Neurosci Methods 60:189–198

    CAS  PubMed  Google Scholar 

  • Unitt J, Hornigold D (2011) Plant lectins are novel Toll-like receptor agonists. Biochem Pharmacol 81:1324–1328

    CAS  PubMed  Google Scholar 

  • Vouldoukis I, Shai Y, Nicolas P, Mor A (1996) Broad spectrum antibiotic activity of the skin-PYY. FEBS Lett 380:237–240

    CAS  PubMed  Google Scholar 

  • 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 116:421–426

    CAS  PubMed  Google Scholar 

  • 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) 131:73–81

    CAS  Google Scholar 

  • 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 202:1527–1538

    CAS  PubMed  Google Scholar 

  • Wheway J, Herzog H, Mackay F (2007) The Y1 receptor for NPY: a key modulator of the adaptive immune system. Peptides 28:453–458

    CAS  PubMed  Google Scholar 

  • 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 23:1901–1908

    CAS  PubMed  Google Scholar 

  • 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 1:315–324

    CAS  PubMed  Google Scholar 

  • 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 24:155–159

    CAS  PubMed  Google Scholar 

  • Zukowska-Grojec Z, Vaz AC (1988) Role of neuropeptide Y (NPY) in cardiovascular responses to stress. Synapse 2:293–298

    CAS  PubMed  Google Scholar 

  • 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 83:187–195

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Institute of Virology, Vaccines and Sera, “Torlak”, Immunology Research Center “Branislav Janković”, Vojvode Stepe 458, 11221, Belgrade, Serbia

    Mirjana Dimitrijević & Stanislava Stanojević

Authors
  1. Mirjana Dimitrijević
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stanislava Stanojević
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mirjana Dimitrijević.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dimitrijević, M., Stanojević, S. The intriguing mission of neuropeptide Y in the immune system. Amino Acids 45, 41–53 (2013). https://doi.org/10.1007/s00726-011-1185-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-011-1185-7

Keywords

Search

Navigation