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Cytokine Interactions with Adrenal Medullary Chromaffin Cells

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Abstract

It is generally accepted that a bi-directional or reciprocal interaction occurs between the immune and neuroendocrine systems, and that this relationship is important for the appropriate physiological functioning of both systems. Similarly, an imbalance in this relationship may contribute to a number of pathologies, most notably those relating to stress. The aim of this article is to consider the interaction of cytokines with the adrenal medulla, a potentially important player in this relationship. The chromaffin cells of the adrenal medulla release catecholamines and a range of biologically active peptides in response to a wide variety of stress-related signals. A growing body of evidence indicates that this stress response is influenced by, and in turn has influence upon, immune signalling. This brief review will focus primarily on the best-described adrenal medullary active cytokines, namely interferon-α, interleukin-6, interleukin-1α/β and tumour necrosis factor-α. In each case, three key issues will be addressed: the physiologically relevant source of the cytokine; the intracellular signalling events arising from activation of its receptor and finally the cellular consequences of such activation in terms of modulation of gene expression and the secretory output of the chromaffin cells.

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References

  • Ait-Ali D, Turquier V, Grumolato L, Yon L, Jourdain M, Alexandre D, Eiden LE, Vaudry H, Anouar Y (2004) The proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 stimulate neuropeptide gene transcription and secretion in adrenochromaffin cells via activation of extracellularly regulated kinase 1/2 and p38 protein kinases, and activator protein-1 transcription factors. Mol Endocrinol 18:1721–1739

    Article  CAS  PubMed  Google Scholar 

  • Ait-Ali D, Turquier V, Tanguy Y et al (2008) Tumor necrosis factor (TNF)-alpha persistently activates nuclear factor-kappaB signaling through the type 2 TNF receptor in chromaffin cells: implications for long-term regulation of neuropeptide gene expression in inflammation. Endocrinology 149:2840–2852

    Article  CAS  PubMed  Google Scholar 

  • Ait-Ali D, Stroth N, Sen JM, Eiden LE (2010) PACAP-cytokine interactions govern adrenal neuropeptide biosynthesis after systemic administration of LPS. Neuropharmacology 58:208–214

    Article  CAS  PubMed  Google Scholar 

  • Alaniz RC, Thomas SA, Perez-Melgosa M, Mueller K, Farr AG, Palmiter RD, Wilson CB (1999) Dopamine beta-hydroxylase deficiency impairs cellular immunity. Proc Natl Acad Sci USA 96:2274–2278

    Article  CAS  PubMed  Google Scholar 

  • Andersson C, Svenson SB, Van Deventer S, Cerami A, Bartfai T (1992) Interleukin-1 alpha expression is inducible by cholinergic stimulation in the rat adrenal gland. Neuroscience 47:481–485

    Article  CAS  PubMed  Google Scholar 

  • Andrade-Mena CE (1996) Catecholamines inhibit alpha/beta interferon production induced by lipopolysaccharide. Regul Pept 65:219–223

    Article  CAS  PubMed  Google Scholar 

  • Andreis PG, Tortorella C, Ziolkowska A, Spinazzi R, Malendowicz LK, Neri G, Nussdorfer GG (2007) Evidence for a paracrine role of endogenous adrenomedullary galanin in the regulation of glucocorticoid secretion in the rat adrenal gland. Int J Mol Med 19:511–515

    CAS  PubMed  Google Scholar 

  • Bobrovskaya L, Dunkley PR, Dickson PW (2004) Phosphorylation of Ser19 increases both Ser40 phosphorylation and enzyme activity of tyrosine hydroxylase in intact cells. J Neurochem 90:857–864

    Article  CAS  PubMed  Google Scholar 

  • Bornstein SR, Haidan A, Ehrhart-Bornstein M (1996) Cellular communication in the neuro-adrenocortical axis: role of vasoactive intestinal polypeptide (VIP). Endocr Res 22:819–829

    CAS  PubMed  Google Scholar 

  • Bunn SJ, Carman F, Douglas S (2009) Interleukin-6 mediated activation of ERK1/2 and STAT3 in adrenal medullary chromaffin cells. Proceedings of the Australian Neuroscience Soc., Canberra, Australia

  • Buske-Kirschbaum A, Gierens A, Hollig H, Hellhammer DH (2002) Stress-induced immunomodulation is altered in patients with atopic dermatitis. J Neuroimmunol 129:161–167

    Article  CAS  PubMed  Google Scholar 

  • Call GB, Husein OF, McIlmoil CJ, Adams A, Heckmann RA, Judd AM (2000) Bovine adrenal cells secrete interleukin-6 and tumor necrosis factor in vitro. Gen Comp Endocrinol 118:249–261

    Article  CAS  PubMed  Google Scholar 

  • Caraglia M, Vitale G, Marra M, Budillon A, Tagliaferri P, Abbruzzese A (2004) Alpha-interferon and its effects on signalling pathways within cells. Curr Protein Pept Sci 5:475–485

    Article  CAS  PubMed  Google Scholar 

  • Cavadas C, Grand D, Mosimann F, Cotrim MD, Fontes Ribeiro CA, Brunner HR, Grouzmann E (2003) Angiotensin II mediates catecholamine and neuropeptide Y secretion in human adrenal chromaffin cells through the AT1 receptor. Regul Pept 111:61–65

    Article  CAS  PubMed  Google Scholar 

  • Charmandari E, Tsigos C, Chrousos G (2005) Endocrinology of the stress response. Annu Rev Physiol 67:259–284

    Article  CAS  PubMed  Google Scholar 

  • Corssmit EP, Heijligenberg R, Endert E, Ackermans MT, Sauerwein HP, Romijn JA (1996) Endocrine and metabolic effects of interferon-alpha in humans. J Clin Endocrinol Metab 81:3265–3269

    Article  CAS  PubMed  Google Scholar 

  • Dafny N, Yang PB (2005) Interferon and the central nervous system. Eur J Pharmacol 523:1–15

    Article  CAS  PubMed  Google Scholar 

  • de Diego AM, Gandia L, Garcia AG (2008) A physiological view of the central and peripheral mechanisms that regulate the release of catecholamines at the adrenal medulla. Acta Physiol (Oxf) 192:287–301

    Article  CAS  Google Scholar 

  • Douglas SA, Bunn SJ (2009) Interferon-alpha signalling in bovine adrenal chromaffin cells: involvement of signal-transducer and activator of transcription 1 and 2, extracellular signal-regulated protein kinases 1/2 and serine 31 phosphorylation of tyrosine hydroxylase. J Neuroendocrinol 21:200–207

    Article  CAS  PubMed  Google Scholar 

  • Elenkov IJ (2008) Neurohormonal-cytokine interactions: implications for inflammation, common human diseases and well-being. Neurochem Int 52:40–51

    Article  CAS  PubMed  Google Scholar 

  • Ershler WB, Keller ET (2000) Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 51:245–270

    Article  CAS  PubMed  Google Scholar 

  • Gadient RA, Lachmund A, Unsicker K, Otten U (1995) Expression of interleukin-6 (IL-6) and IL-6 receptor mRNAs in rat adrenal medulla. Neurosci Lett 194:17–20

    Article  CAS  PubMed  Google Scholar 

  • Ganea D, Delgado M (2002) Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity. Crit Rev Oral Biol Med 13:229–237

    Article  PubMed  Google Scholar 

  • Gonzalez-Hernandez JA, Bornstein SR, Ehrhart-Bornstein M, Spath-Schwalbe E, Jirikowski G, Scherbaum WA (1994) Interleukin-6 messenger ribonucleic acid expression in human adrenal gland in vivo: new clue to a paracrine or autocrine regulation of adrenal function. J Clin Endocrinol Metab 79:1492–1497

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Hernandez JA, Ehrhart-Bornstein M, Spath-Schwalbe E, Scherbaum WA, Bornstein SR (1996) Human adrenal cells express tumor necrosis factor-alpha messenger ribonucleic acid: evidence for paracrine control of adrenal function. J Clin Endocrinol Metab 81:807–813

    Article  CAS  PubMed  Google Scholar 

  • Goshen I, Yirmiya R (2009) Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 30:30–45

    Article  CAS  PubMed  Google Scholar 

  • Gwosdow AR (1995) Mechanisms of interleukin-1-induced hormone secretion from the rat adrenal gland. Endocr Res 21:25–37

    Article  CAS  PubMed  Google Scholar 

  • Houghtling RA, Bayer BM (2002) Rapid elevation of plasma interleukin-6 by morphine is dependent on autonomic stimulation of adrenal gland. J Pharmacol Exp Ther 300:213–219

    Article  CAS  PubMed  Google Scholar 

  • Jaattela M, Carpen O, Stenman UH, Saksela E (1990) Regulation of ACTH-induced steroidogenesis in human fetal adrenals by rTNF-alpha. Mol Cell Endocrinol 68:R31–R36

    Article  CAS  PubMed  Google Scholar 

  • Judd AM, MacLeod RM (1995) Differential release of tumor necrosis factor and IL-6 from adrenal zona glomerulosa cells in vitro. Am J Physiol 268:E114–E120

    CAS  PubMed  Google Scholar 

  • Kavelaars A, Kuis W, Knook L, Sinnema G, Heijnen CJ (2000) Disturbed neuroendocrine-immune interactions in chronic fatigue syndrome. J Clin Endocrinol Metab 85:692–696

    Article  CAS  PubMed  Google Scholar 

  • Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB (1995) The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 95:2111–2119

    Article  CAS  PubMed  Google Scholar 

  • Kumai T, Tateishi T, Tanaka M, Watanabe M, Shimizu H, Kobayashi S (2000) Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats. Life Sci 67:663–669

    Article  CAS  PubMed  Google Scholar 

  • Kunioku H, Inoue K, Tomida M (2001) Interleukin-6 protects rat PC12 cells from serum deprivation or chemotherapeutic agents through the phosphatidylinositol 3-kinase and STAT3 pathways. Neurosci Lett 309:13–16

    Article  CAS  PubMed  Google Scholar 

  • Kunz D, Walker G, Bedoucha M, Certa U, Marz-Weiss P, Dimitriades-Schmutz B, Otten U (2009) Expression profiling and Ingenuity biological function analyses of interleukin-6-versus nerve growth factor-stimulated PC12 cells. BMC Genomics 10:90

    Article  PubMed  CAS  Google Scholar 

  • Kuri BA, Chan SA, Smith CB (2009) PACAP regulates immediate catecholamine release from adrenal chromaffin cells in an activity-dependent manner through a protein kinase C-dependent pathway. J Neurochem 110:1214–1225

    Article  CAS  PubMed  Google Scholar 

  • Maggio M, Guralnik JM, Longo DL, Ferrucci L (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61:575–584

    PubMed  Google Scholar 

  • Marley PD (2003) Mechanisms in histamine-mediated secretion from adrenal chromaffin cells. Pharmacol Ther 98:1–34

    Article  CAS  PubMed  Google Scholar 

  • McGillis JP, Mitsuhashi M, Payan DG (1990) Immunomodulation by tachykinin neuropeptides. Ann N Y Acad Sci 594:85–94

    Article  CAS  PubMed  Google Scholar 

  • Morita K, Miyasako T, Kitayama S, Dohi T (2004) Interleukin-1 inhibits voltage-dependent P/Q-type Ca2+ channel associated with the inhibition of the rise of intracellular free Ca2+ concentration and catecholamine release in adrenal chromaffin cells. Biochim Biophys Acta 1673:160–169

    CAS  PubMed  Google Scholar 

  • Mravec B (2005) A new focus on interoceptive properties of adrenal medulla. Auton Neurosci 120:10–17

    Article  CAS  PubMed  Google Scholar 

  • Nobel CS, Schultzberg M (1995) Induction of interleukin-1 beta mRNA and enkephalin mRNA in the rat adrenal gland by lipopolysaccharides studied by in situ hybridization histochemistry. Neuroimmunomodulation 2:61–73

    Article  CAS  PubMed  Google Scholar 

  • Nussdorfer GG, Mazzocchi G (1998) Immune-endocrine interactions in the mammalian adrenal gland: facts and hypotheses. Int Rev Cytol 183:143–184

    Article  CAS  PubMed  Google Scholar 

  • O’Brien SM, Scott LV, Dinan TG (2004) Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 19:397–403

    Article  PubMed  CAS  Google Scholar 

  • Path G, Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA (1997) Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis. J Clin Endocrinol Metab 82:2343–2349

    Article  CAS  PubMed  Google Scholar 

  • Path G, Scherbaum WA, Bornstein SR (2000) The role of interleukin-6 in the human adrenal gland. Eur J Clin Invest 30(Suppl 3):91–95

    Article  CAS  PubMed  Google Scholar 

  • Perez-Rodriguez R, Fuentes MP, Olivan AM, Martinez-Palacian A, Roncero C, Gonzalez MP, Oset-Gasque MJ (2007) Mechanisms of nitric oxide-induced apoptosis in bovine chromaffin cells: role of mitochondria and apoptotic proteins. J Neurosci Res 85:2224–2238

    Article  CAS  PubMed  Google Scholar 

  • Perez-Rodriguez R, Roncero C, Olivan AM, Gonzalez MP, Oset-Gasque MJ (2009) Signaling mechanisms of interferon gamma induced apoptosis in chromaffin cells: involvement of nNOS, iNOS, and NFkappaB. J Neurochem 108:1083–1096

    Article  CAS  PubMed  Google Scholar 

  • Pestka S, Krause CD, Walter MR (2004) Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202:8–32

    Article  CAS  PubMed  Google Scholar 

  • Rosmaninho-Salgado J, Alvaro AR, Grouzmann E, Duarte EP, Cavadas C (2007) Neuropeptide Y regulates catecholamine release evoked by interleukin-1beta in mouse chromaffin cells. Peptides 28:310–314

    Article  CAS  PubMed  Google Scholar 

  • Rosmaninho-Salgado J, Araujo IM, Alvaro AR, Mendes AF, Ferreira L, Grouzmann E, Mota A, Duarte EP, Cavadas C (2009) Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin-1beta: role of neuropeptide Y and nitric oxide. J Neurochem 109:911–922

    Article  CAS  PubMed  Google Scholar 

  • Sacerdote P, Gaspani L, Panerai AE (2001) Role of beta-endorphin in the modulation of immune responses: perspectives in autoimmune diseases. Adv Exp Med Biol 493:137–142

    Article  CAS  PubMed  Google Scholar 

  • Satoh T, Nakamura S, Taga T, Matsuda T, Hirano T, Kishimoto T, Kaziro Y (1988) Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. Mol Cell Biol 8:3546–3549

    CAS  PubMed  Google Scholar 

  • Schinner S, Bornstein SR (2005) Cortical-chromaffin cell interactions in the adrenal gland. Endocr Pathol 16:91–98

    Article  CAS  PubMed  Google Scholar 

  • Schultzberg M, Andersson C, Unden A, Troye-Blomberg M, Svenson SB, Bartfai T (1989) Interleukin-1 in adrenal chromaffin cells. Neuroscience 30:805–810

    Article  CAS  PubMed  Google Scholar 

  • Schultzberg M, Tingsborg S, Nobel S, Lundkvist J, Svenson S, Simoncsits A, Bartfai T (1995) Interleukin-1 receptor antagonist protein and mRNA in the rat adrenal gland. J Interf Cytokine Res 15:721–729

    Article  CAS  Google Scholar 

  • Song M, Kellum JA (2005) Interleukin-6. Crit Care Med 33:S463–S465

    Article  PubMed  Google Scholar 

  • Spulber S, Schultzberg M (2009) Connection between inflammatory processes and transmittor function-modulatory effects of interleukin-1. Prog Neurobiol 90:256–262

    Article  PubMed  CAS  Google Scholar 

  • Straub RH (2006) Bottom-up and top-down signaling of IL-6 with and without habituation? Brain Behav Immun 20:37–39

    Article  CAS  PubMed  Google Scholar 

  • Stroth N, Eiden LE (2010) Stress hormone synthesis in mouse hypothalamus and adrenal gland triggered by restraint is dependent on pituitary adenylate cyclase-activating polypeptide signaling. Neuroscience 165:1025–1030

    Article  CAS  PubMed  Google Scholar 

  • Tachikawa E, Kondo Y, Takahashi M, Kashimoto T, Yanagihara N, Toyohira Y, Izumi F (1997) Interferon-alpha reduces catecholamine secretion from bovine adrenal chromaffin cells stimulated by acetylcholine. Naunyn Schmiedebergs Arch Pharmacol 356:699–705

    Article  CAS  PubMed  Google Scholar 

  • Tchelingerian JL, Le Saux F, Jacque C (1996) Identification and topography of neuronal cell populations expressing TNF alpha and IL-1 alpha in response to hippocampal lesion. J Neurosci Res 43:99–106

    Article  CAS  PubMed  Google Scholar 

  • Toyohira Y, Yanagihara N, Minami K, Ueno S, Uezono Y, Tachikawa E, Kondo Y, Kashimoto T, Izumi F (1998) Down-regulation of the noradrenaline transporter by interferon-alpha in cultured bovine adrenal medullary cells. J Neurochem 70:1441–1447

    Article  CAS  PubMed  Google Scholar 

  • Turquier V, Vaudry H, Yon L, Hsu CM, Ait-Ali D, Grumolato L, Eiden LE, Anouar Y (2002) Proinflammatory cytokines TNF-alpha and IL-1alpha stimulate neuropeptide gene expression in adrenochromaffin cells. Ann N Y Acad Sci 971:45–48

    Article  CAS  PubMed  Google Scholar 

  • Yanagihara N, Minami K, Shirakawa F, Uezono Y, Kobayashi H, Eto S, Izumi F (1994) Stimulatory effect of IL-1 beta on catecholamine secretion from cultured bovine adrenal medullary cells. Biochem Biophys Res Commun 198:81–87

    Article  CAS  PubMed  Google Scholar 

  • Zhou D, Kusnecov AW, Shurin MR, DePaoli M, Rabin BS (1993) Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis. Endocrinology 133:2523–2530

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Stephen J. Bunn.

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A commentary to this article can be found at doi:10.1007/s10571-010-9607-8.

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Douglas, S.A., Sreenivasan, D., Carman, F.H. et al. Cytokine Interactions with Adrenal Medullary Chromaffin Cells. Cell Mol Neurobiol 30, 1467–1475 (2010). https://doi.org/10.1007/s10571-010-9593-x

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