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. 1988 Mar 1;167(3):924–936. doi: 10.1084/jem.167.3.924

Induction of high-affinity interleukin 1 receptor on human peripheral blood lymphocytes by glucocorticoid hormones

PMCID: PMC2188871  PMID: 2965211

Abstract

The in vitro effect of glucocorticoids (GCs) on IL-1-R expression of human PBMCs was investigated. Both physiological and pharmacological concentration ranges of GC increased the specific binding of 125I- labeled human rIL-1 alpha to PBMCs. This enhancement was specific for GC, since other steroid hormones, such as progesterone, 17 beta- estradiol, and testosterone failed to elevate the binding of 125I-IL-1 alpha to PBMCs. The effect was time dependent with maximal effect occurring 6 h after treatment and dose dependent with half-maximal effect elicited by 100 nM prednisolone. Scatchard plot analysis indicated that 125I-IL-1 alpha binding increased from approximately 100 IL-1-R per cell to 2 X 10(3) receptors per cell without a major change in affinity (Kd = 2.6 X 10(-10) M). The subpopulation of PBMCs induced by GC to express higher levels of IL-1-R consisted predominantly of B lymphocytes, but not T lymphocytes, large granular lymphocytes, or monocytes. GCs also induced the expression of IL-1-R on some other cell types, including normal human dermal fibroblasts and the human large granular lymphocyte cell line YT. Since cycloheximide and actinomycin D inhibited the induction of IL-1-R by GC, synthesis of both new RNA and protein seems to be required for IL-1-R induction. This study presents the first evidence of upregulation of the receptors for IL-1 by GC, and may account for the reported enhancement of in vitro and in vivo humoral immune responses by GCs.

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Selected References

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  1. Akiyama Y., Miller P. J., Thurman G. B., Neubauer R. H., Oliver C., Favilla T., Beman J. A., Oldham R. K., Stevenson H. C. Characterization of a human blood monocyte subset with low peroxidase activity. J Clin Invest. 1983 Sep;72(3):1093–1105. doi: 10.1172/JCI111034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker J. B., Barsh G. S., Carney D. H., Cunningham D. D. Dexamethasone modulates binding and action of epidermal growth factor in serum-free cell culture. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1882–1886. doi: 10.1073/pnas.75.4.1882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balow J. E., Hurley D. L., Fauci A. S. Immunosuppressive effects of glucocorticosteroids: differential effects of acute vs chronic administration on cell-mediated immunity. J Immunol. 1975 Mar;114(3):1072–1076. [PubMed] [Google Scholar]
  4. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braun T., Hechter O. Glucocorticoid regulation of ACTH sensitivity of adenyl cyclase in rat fat cell membranes. Proc Natl Acad Sci U S A. 1970 Jul;66(3):995–1001. doi: 10.1073/pnas.66.3.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Butler W. T., Rossen R. D. Effects of corticosteroids on immunity in man. I. Decreased serum IgG concentration caused by 3 or 5 days of high doses of methylprednisolone. J Clin Invest. 1973 Oct;52(10):2629–2640. doi: 10.1172/JCI107455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Claman H. N. Corticosteroids and lymphoid cells. N Engl J Med. 1972 Aug 24;287(8):388–397. doi: 10.1056/NEJM197208242870806. [DOI] [PubMed] [Google Scholar]
  8. Claman H. N., Moorhead J. W., Benner W. H. Corticosteroids and lymphoid cells in vitro. I. Hydrocortisone lysis of human, guinea pig, and mouse thymus cells. J Lab Clin Med. 1971 Oct;78(4):499–507. [PubMed] [Google Scholar]
  9. Dinarello C. A., Marnoy S. O., Rosenwasser L. J. Role of arachidonate metabolism in the immunoregulatory function of human leukocytic pyrogen/lymphocyte-activating factor/interleukin 1. J Immunol. 1983 Feb;130(2):890–895. [PubMed] [Google Scholar]
  10. Dower S. K., Kronheim S. R., March C. J., Conlon P. J., Hopp T. P., Gillis S., Urdal D. L. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med. 1985 Aug 1;162(2):501–515. doi: 10.1084/jem.162.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fantus I. G., Saviolakis G. A., Hedo J. A., Gorden P. Mechanism of glucocorticoid-induced increase in insulin receptors of cultured human lymphocytes. J Biol Chem. 1982 Jul 25;257(14):8277–8283. [PubMed] [Google Scholar]
  12. Fauci A. S., Dale D. C., Balow J. E. Glucocorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med. 1976 Mar;84(3):304–315. doi: 10.7326/0003-4819-84-3-304. [DOI] [PubMed] [Google Scholar]
  13. Fauci A. S., Dale D. C. The effect of in vivo hydrocortisone on subpopulations of human lymphocytes. J Clin Invest. 1974 Jan;53(1):240–246. doi: 10.1172/JCI107544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fauci A. S., Pratt K. R., Whalen G. Activation of human B lymphocytes. IV. Regulatory effects of corticosteroids on the triggering signal in the plaque-forming cell response of human peripheral blood B lymphocytes to polyclonal activation. J Immunol. 1977 Aug;119(2):598–603. [PubMed] [Google Scholar]
  15. Gerrard T. L., Cupps T. R., Jurgensen C. H., Fauci A. S. Hydrocortisone-mediated inhibition of monocyte antigen presentation: dissociation of inhibitory effect and expression of DR antigens. Cell Immunol. 1984 May;85(2):330–339. doi: 10.1016/0008-8749(84)90247-8. [DOI] [PubMed] [Google Scholar]
  16. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gillis S., Crabtree G. R., Smith K. A. Glucocorticoid-induced inhibition of T cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation. J Immunol. 1979 Oct;123(4):1624–1631. [PubMed] [Google Scholar]
  18. Grayson J., Dooley N. J., Koski I. R., Blaese R. M. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes. J Clin Invest. 1981 Dec;68(6):1539–1547. doi: 10.1172/JCI110408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. HAVENS W. P., Jr, SHAFFER J. M., HOPKE C. J., Jr The effect of ACTH and cortisone on the concentration of circulating diphtheria antitoxin. J Immunol. 1952 Apr;68(4):389–400. [PubMed] [Google Scholar]
  20. Hattori T., Hirata F., Hoffman T., Hizuta A., Herberman R. B. Inhibition of human natural killer (NK) activity and antibody dependent cellular cytotoxicity (ADCC) by lipomodulin, a phospholipase inhibitory protein. J Immunol. 1983 Aug;131(2):662–665. [PubMed] [Google Scholar]
  21. Hill M. R., Stith R. D., McCallum R. E. Interleukin 1: a regulatory role in glucocorticoid-regulated hepatic metabolism. J Immunol. 1986 Aug 1;137(3):858–862. [PubMed] [Google Scholar]
  22. Howard M., Mizel S. B., Lachman L., Ansel J., Johnson B., Paul W. E. Role of interleukin 1 in anti-immunoglobulin-induced B cell proliferation. J Exp Med. 1983 May 1;157(5):1529–1543. doi: 10.1084/jem.157.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ilfeld D. N., Krakauer R. S., Blaese R. M. Suppression of the human autologous mixed lymphocyte reaction by physiologic concentrations of hydrocortisone. J Immunol. 1977 Aug;119(2):428–434. [PubMed] [Google Scholar]
  24. Lipsky P. E., Thompson P. A., Rosenwasser L. J., Dinarello C. A. The role of interleukin 1 in human B cell activation: inhibition of B cell proliferation and the generation of immunoglobulin-secreting cells by an antibody against human leukocytic pyrogen. J Immunol. 1983 Jun;130(6):2708–2714. [PubMed] [Google Scholar]
  25. Logsdon C. D. Glucocorticoids increase cholecystokinin receptors and amylase secretion in pancreatic acinar AR42J cells. J Biol Chem. 1986 Feb 15;261(5):2096–2101. [PubMed] [Google Scholar]
  26. Matsushima K., Akahoshi T., Yamada M., Furutani Y., Oppenheim J. J. Properties of a specific interleukin 1 (IL 1) receptor on human Epstein Barr virus-transformed B lymphocytes: identity of the receptor for IL 1-alpha and IL 1-beta. J Immunol. 1986 Jun 15;136(12):4496–4502. [PubMed] [Google Scholar]
  27. Matsushima K., Kobayashi Y., Copeland T. D., Akahoshi T., Oppenheim J. J. Phosphorylation of a cytosolic 65-kDa protein induced by interleukin 1 in glucocorticoid pretreated normal human peripheral blood mononuclear leukocytes. J Immunol. 1987 Nov 15;139(10):3367–3374. [PubMed] [Google Scholar]
  28. Murphy P. A., Simon P. L., Willoughby W. F. Endogenous pyrogens made by rabbit peritoneal exudate cells are identical with lymphocyte-activating factors made by rabbit alveolar macrophages. J Immunol. 1980 May;124(5):2498–2501. [PubMed] [Google Scholar]
  29. NOWELL P. C. Inhibition of human leukocyte mitosis by prednisolone in vitro. Cancer Res. 1961 Dec;21:1518–1521. [PubMed] [Google Scholar]
  30. Ortaldo J. R., Mason A., Overton R. Lymphokine-activated killer cells. Analysis of progenitors and effectors. J Exp Med. 1986 Oct 1;164(4):1193–1205. doi: 10.1084/jem.164.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reed J. C., Abidi A. H., Alpers J. D., Hoover R. G., Robb R. J., Nowell P. C. Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. J Immunol. 1986 Jul 1;137(1):150–154. [PubMed] [Google Scholar]
  32. Rhodes J., Ivanyi J., Cozens P. Antigen presentation by human monocytes: effects of modifying major histocompatibility complex class II antigen expression and interleukin 1 production by using recombinant interferons and corticosteroids. Eur J Immunol. 1986 Apr;16(4):370–375. doi: 10.1002/eji.1830160410. [DOI] [PubMed] [Google Scholar]
  33. Rinehart J. J., Wuest D., Ackerman G. A. Corticosteroid alteration of human monocyte to macrophage differentiation. J Immunol. 1982 Oct;129(4):1436–1440. [PubMed] [Google Scholar]
  34. Schmidt J. A., Mizel S. B., Cohen D., Green I. Interleukin 1, a potential regulator of fibroblast proliferation. J Immunol. 1982 May;128(5):2177–2182. [PubMed] [Google Scholar]
  35. Sipe J. D., Vogel S. N., Ryan J. L., McAdam K. P., Rosenstreich D. L. Detection of a mediator derived from endotoxin-stimulated macrohpages that induces the acute phase serum amyloid A response in mice. J Exp Med. 1979 Sep 19;150(3):597–606. doi: 10.1084/jem.150.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Smith R. S., Sherman N. A., Middleton E., Jr Effect of hydrocortisone on immunoglobulin synthesis and secretion by human peripheral lymphocytes in vitro. Int Arch Allergy Appl Immunol. 1972;43(6):859–870. doi: 10.1159/000230903. [DOI] [PubMed] [Google Scholar]
  37. Snyder D. S., Unanue E. R. Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production. J Immunol. 1982 Nov;129(5):1803–1805. [PubMed] [Google Scholar]
  38. Tuchinda M., Newcomb R. W., DeVald B. L. Effect of prednisone treatment on the human immune response to keyhole limpet hemocyanin. Int Arch Allergy Appl Immunol. 1972;42(4):533–544. doi: 10.1159/000230634. [DOI] [PubMed] [Google Scholar]
  39. Turnell R. W., Kaiser N., Milholland R. J., Rosen F. Glucocorticoid receptors in rat thymocytes. Interactions with the antiglucocorticoid cortexolone and mechanism of its action. J Biol Chem. 1974 Feb 25;249(4):1133–1138. [PubMed] [Google Scholar]
  40. Vischer T. L. Effect of hydrocortisone on the reactivity of thymus and spleen cells of mice to in vitro stimulation. Immunology. 1972 Nov;23(5):777–784. [PMC free article] [PubMed] [Google Scholar]
  41. Woloski B. M., Smith E. M., Meyer W. J., 3rd, Fuller G. M., Blalock J. E. Corticotropin-releasing activity of monokines. Science. 1985 Nov 29;230(4729):1035–1037. doi: 10.1126/science.2997929. [DOI] [PubMed] [Google Scholar]
  42. Yodoi J., Teshigawara K., Nikaido T., Fukui K., Noma T., Honjo T., Takigawa M., Sasaki M., Minato N., Tsudo M. TCGF (IL 2)-receptor inducing factor(s). I. Regulation of IL 2 receptor on a natural killer-like cell line (YT cells). J Immunol. 1985 Mar;134(3):1623–1630. [PubMed] [Google Scholar]

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