Calcified Tissue International

, Volume 55, Issue 2, pp 109–113 | Cite as

Regulation of lymphocyte calcitonin receptors by interleukin-1 and interleukin-6

  • J. J. Body
  • G. Fernandez
  • M. Lacroix
  • P. Vandenbussche
  • J. Content
Laboratory Investigations

Abstract

We have reported the existence of specific and high-affinity calcitonin (CT) receptors on normal human T-lymphocytes. Because of the increasingly recognized importance of interleukin-1 (IL-1) and IL-6 in the control of bone metabolism, we have examined their influence on the binding parameters of labeled salmon calcitonin (sCT) on lymphocytes. After a 24-hour incubation, IL-1 at 100–5000 U/ml and IL-6, at 1–1000 U/ml, decreased the apparent number of CT binding sites (Bmax) on T-lymphocytes. The effects of IL-6 on purified T-lymphocytes were dose related and 100 U of IL-6/ml reduced sCT binding to 57±16% (mean ± SD) of the control values (n=6). There was no significant change in CT binding affinity (Kd, 0.71±0.54x10-10 M for controls versus 0.90±0.55x10-10 M after IL-6) and the decrease in Bmax was reversible after 48 hours. The effects of IL-1 appeared to be mediated through an increased production of IL-6 as they were neutralized by a polyclonal antiserum against IL-6. Added alone, the antiserum caused a slight increase in the apparent number of CT binding sites on T-lymphocytes to 115±5% of control values (n=3). In summary, IL-1 and IL-6 can induce a marked apparent loss of CT binding sites on normal T-lymphocytes at concentrations known to be active on bone metabolism. The contributions of our observations to the osteolytic activity of these cytokines deserve further investigation.

Key words

Calcitonin Interleukin-6 Cytokine Bone resorption Lymphocyte 

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References

  1. 1.
    Nicholson GC, Moseley JM, Sexton PM, Mendelsohn FAO, Martin TJ (1986) Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest 78:355–360Google Scholar
  2. 2.
    Tashjian AH Jr, Wright DR, Ivey JL, Pont A (1978) Calcitonin binding sites in bone: relationships to biological response and “escape”. Recent Prog Horm Res 34:285–334Google Scholar
  3. 3.
    Body JJ, Glibert F, Nejai S, Fernandez G, Van Langendonck A, Borkowski A (1990) Calcitonin receptors on circulating normal human lymphocytes. J Clin Endocrinol Metab 71:675–681Google Scholar
  4. 4.
    Adami S, Suppi R, Residori M, Braga V, Zamboni M, LoCascio V (1988) Intramuscular administration of salmon calcitonin impairs delayed cutaneous hypersensitivity. Bone Miner 4:91–94Google Scholar
  5. 5.
    Van Snick J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278Google Scholar
  6. 6.
    Nguyen L, Dewhirst FE, Hauschka PV, Stashenko P (1991) Interleukin-1β stimulates bone resorption and inhibits bone formation in vivo. Lymphokine Cytokine Res 10:15–21Google Scholar
  7. 7.
    Pfeilschifter J, Chenu C, Bird A, Mundy GR, Roodman GD (1989) Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. J Bone Miner Res 4:113–118Google Scholar
  8. 8.
    Evans DB, Bunning RAD, Russell RGG (1990) The effects of recombinant human interleukin-1β on cellular proliferation and the production of prostaglandin E2, plasminogen activator, osteocalcin and alkaline phosphatase by osteoblast-like cells derived from human bone. Biochem Biophys Res Commun 166: 208–216Google Scholar
  9. 9.
    Nowak RA, Morrison NE, Goad DL, Gaffney EV, Tashjian AH Jr (1990) Squamous cell carcinomas often produce more than a single bone resorption-stimulating factor: role of interleukin-1α. Endocrinology 127:3061–3069Google Scholar
  10. 10.
    Pacifici R, Rifas L, Teitelbaum S, Slatopolsky E, McCraken R, Bergfeld M, Lee W, Avioli LV, Peck WA (1987) Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. Proc Natl Acad Sci 84:4616–4620Google Scholar
  11. 11.
    Roodman GD (1992) Interleukin-6: an osteotropic factor? J Bone Miner Res 7:475–478Google Scholar
  12. 12.
    Girasole G, Jilka RL, Passeri G, Boswell S, Boder G, Williams DC, Manolagas SC (1992) 17β-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest 89:883–891Google Scholar
  13. 13.
    Scatchard O, (1949) The attraction of proteins for small molecules and ions. Ann NY Acad Sci 50:660–672Google Scholar
  14. 14.
    Muson PJ, Rodbard D (1980) Ligand: a versatile computerized approach for characterization of Ligand-binding systems. Anal Biochem 107:220–239Google Scholar
  15. 15.
    Devière J, Content J, Denys C, Vandenbussche P, Le Moine O, Shandene L, Vaerman JP, Dupont E (1992) Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics. Gastroenterology 103:1296–1301Google Scholar
  16. 16.
    Tosato G, Jones KD (1990) Interleukin-1 induces interleukin-6 production in peripheral blood monocytes. Blood 75:1305–1310Google Scholar
  17. 17.
    Sironi M, Breviario F, Proserpio P, Biondi A, Vecchi A, Van Damme J, Dejana E, Mantovani A (1989) IL-1 stimulates IL-6 production in endothelial cells. J Immunol 142:549–553Google Scholar
  18. 18.
    Bender S, Haubeck HD, Van de Leur E, Dufhues G, Schiel X, Lauwerijns J, Greiling H, Heinrich PC (1990) Interleukin-1β induces synthesis and secretion of interleukin-6 in human chondrocytes. FEBS Lett 263:321–324Google Scholar
  19. 19.
    Spangelo BL, Jarvis WD, Judd AM, MacLeod RM (1991) Induction of interleukin-6 release by interleukin-1 in rat anterior pituitary cells in vitro: evidence for an eicosanoid-dependent mechanism. Endocrinology 129:2886–2894Google Scholar
  20. 20.
    Linkhart TA, Linkhart SG, MacCharles DC, Long DL, Strong DD (1991) Interleukin-6 messenger RNA expression and interleukin-6 protein secretion in cells isolated from normal human bone: regulation by inerleukin-1. J Bone Miner Res 6:1285–1294Google Scholar
  21. 21.
    Littlewood AJ, Russell J, Harvey GR, Hughes DE, Russell RGG, Gowen M (1991) The modulation of the expression of IL-6 and its receptor in human osteoblasts in vitro. Endocrinology 129:1513–1520Google Scholar
  22. 22.
    Löwik CWGM, van der Pluijm G, Bloys H, Hoekman K, Bijvoet OLM, Aarden LA, Papapoulos SE, (1989) Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: a possible role of interleukin-6 in osteoclastogenesis. Biochem Biophys Res Commun 162:1546–1552Google Scholar
  23. 23.
    Ming JE, Granelli-Piperno A (1990) Distinctive features in the production of IL-6 by human T cells. Cell Immunol 130:437–445Google Scholar
  24. 24.
    Zola H, Flego L (1992) Expression of interleukin-6 receptor on blood lymphocytes without in vitro activation. Immunology 76: 338–340Google Scholar
  25. 25.
    Nong YH, Titus RG, Ribeiro JMC, Remold HG (1989) Peptides encoded by the calcitonin gene inhibit macrophage function. J Immunol 143:45–49Google Scholar
  26. 26.
    Mulder H, van Bolhuis H, Naafs MAB, Winckers PLM (1985) Influence of pharmacological doses of calcitonin on serum β2 microglobulin concentration. Calcif Tissue Int 37:367–371Google Scholar
  27. 27.
    Rapado A, Yague M, Diaz Curiel M, Ortiz F, Palomino P, de la Piedra C, Torres R, Peramo B, Lopez Gavilanes E (1991) Cellular immunodeficiency in Paget's disease of bone: changes induced by treatment with Elcatonin. Calcif Tissue Int. 49:436–437Google Scholar
  28. 28.
    McGillis JP, Humphreys S, Reid S (1991) Characterization of functional calcitonin gene-related peptide receptors on rat lymphocytes. J Immunol 147:3482–3489Google Scholar
  29. 29.
    Umeda Y, Arisawa M (1989) Characterization of the calcitonin gene-related peptide receptor in mouse T-lymphocytes. Neuropeptides 14:237–242Google Scholar
  30. 30.
    Umeda Y, Takamiya M, Yoshizaki H, Arisawa M (1988) Inhibition of mitogen-stimulated T lymphocyte proliferation by calcitonin gene-related peptide. Biochem Biophys Res Commun 154:227–235Google Scholar
  31. 31.
    Boudard F, Bastide M (1991) Inhibition of mouse T-cell proliferation by CGRP and VIP: effects of these neuropeptides on IL-2 production and cAMP synthesis. J Neurosci Res 29:29–41Google Scholar
  32. 32.
    Kurihara N, Bertolini D, Suda T, Akiyama Y, Roodman GD (1990) IL-6 stimulates osteoclast-like multinucleated cell formation in long-term human marrow cultures by inducing IL-1 release. J Immunol 144:4226–4230Google Scholar
  33. 33.
    Black K, Garrett IR, Mundy GR, (1991) Chinese hamster ovarian cells transfected with the murine Interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice. Endocrinology 128:2657–2659Google Scholar
  34. 34.
    Koren R, Ravid A, Liberman UA, Hochberg Z, Weisman Y, Novogrodsky A (1985) Defective binding and function of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with end-organ resistance to 1,25-dihydroxyvitamin D. J Clin Invest 76:2012–2015Google Scholar
  35. 35.
    Olmos JM, Amado JA, Riancho JA, Albajar M, Gonzalez-Macias J (1990) Sex and age distribution of 1,25(OH)2D3 receptors in peripheral blood mononuclear cells from normal human subjects. Bone 11:407–409Google Scholar
  36. 36.
    Koren R, Ravid A, Liberman UA (1992) Peripheral blood mononuclear cells: a model for the human vitamin D endocrine system in health and disease. Mol Cell Endocrinol 83:C9-C12Google Scholar
  37. 37.
    Keeting PE, Rifas L, Harris SA, Colvard DS, Spelsberg TC, Peck WA, Riggs BL (1991) Evidence for interleukin-1β production by cultured normal human osteoblast-like cells. J Bone Miner Res 6:827–833Google Scholar
  38. 38.
    Bataille R, Jourdan M, Zhang XG, Klein B (1989) Serum levels of interleukin-6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. J Clin Invest 84:2008–2011Google Scholar
  39. 39.
    Pacifici R, Brown C, Puscheck E, Friedrich E, Slatopolsky E, Maggio D, McCracken R, avioli LV (1991) Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells. Proc Natl Acad Sci USA 88:5134–5138Google Scholar
  40. 40.
    Jilka RL, Hangoc G, Girasole G, Passeri G, Williams D, Abrams JS, Boyce B, Boxmeyer H, Manolagas SC (1992) Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science 257:88–91Google Scholar
  41. 41.
    Passeri G, Girasole G, Jilka RL, Manolagas SC (1993) Increased Interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal. Endocrinology 133:822–828Google Scholar

Copyright information

© Springer-Verlag New York Inc 1994

Authors and Affiliations

  • J. J. Body
    • 1
    • 2
  • G. Fernandez
    • 1
    • 2
  • M. Lacroix
    • 1
    • 2
  • P. Vandenbussche
    • 3
  • J. Content
    • 3
  1. 1.Bone Metabolism Unit, Service de Médecine, Institut J. BordetUniversité Libre de BruxellesBrusselsBelgium
  2. 2.Laboratoire d'Investigation Clinique H.J. Tagnon, Institut J. BordetUniversité Libre de BruxellesBrusselsBelgium
  3. 3.Institut Pasteur du BrabantBrusselsBelgium

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