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. 1992 Nov;77(3):436–442.

Regulation of production of adrenocorticotropin-like proteins in human mononuclear cells.

A T Reder 1
PMCID: PMC1421713  PMID: 1335962

Abstract

Cells of the immune system produce biologically active adrenocorticotropic hormone (ACTH). Many laboratories, however, have been unable to replicate experiments which demonstrate ACTH in immune cells. Sensitive immunohistochemical staining and digital scanning, confocal microscopy were used to study regulation of ACTH-like immunoreactivity (ACTH-IR) in human mononuclear cells. Cytoplasmic ACTH-IR was induced by corticotrophin releasing factor (CRF)/arginine vasopressin (AVP), and also by protein kinase C (PKC) activation and by the interferon (IFN-alpha beta inducer, Na-polyinosinic-polycytidylic acid (polyIC). Induction of cytoplasmic ACTH-IR was maximal within 6 hr of stimulation with CRF/AVP or phorbol myristate acetate (PMA). Recombinant human interleukin-1 beta (rhIL-1 beta) was also stimulatory, but rhIL-1 alpha had minimal effect. Regulation of ACTH-IR production in immune cells parallels the regulation of ACTH in the anterior pituitary, and ACTH-like material may affect immune responses.

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Selected References

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  1. Alvarez-Mon M., Kehrl J. H., Fauci A. S. A potential role for adrenocorticotropin in regulating human B lymphocyte functions. J Immunol. 1985 Dec;135(6):3823–3826. [PubMed] [Google Scholar]
  2. Bernardini R., Kamilaris T. C., Calogero A. E., Johnson E. O., Gomez M. T., Gold P. W., Chrousos G. P. Interactions between tumor necrosis factor-alpha, hypothalamic corticotropin-releasing hormone, and adrenocorticotropin secretion in the rat. Endocrinology. 1990 Jun;126(6):2876–2881. doi: 10.1210/endo-126-6-2876. [DOI] [PubMed] [Google Scholar]
  3. Berry N., Nishizuka Y. Protein kinase C and T cell activation. Eur J Biochem. 1990 Apr 30;189(2):205–214. doi: 10.1111/j.1432-1033.1990.tb15478.x. [DOI] [PubMed] [Google Scholar]
  4. Bilezikjian L. M., Woodgett J. R., Hunter T., Vale W. W. Phorbol ester-induced down-regulation of protein kinase C abolishes vasopressin-mediated responses in rat anterior pituitary cells. Mol Endocrinol. 1987 Aug;1(8):555–560. doi: 10.1210/mend-1-8-555. [DOI] [PubMed] [Google Scholar]
  5. Bost K. L., Clarke B. L., Xu J. C., Kiyono H., McGhee J. R., Pascual D. Modulation of IgM secretion and H chain mRNA expression in CH12.LX.C4.5F5 B cells by adrenocorticotropic hormone. J Immunol. 1990 Dec 15;145(12):4326–4331. [PubMed] [Google Scholar]
  6. Breder C. D., Dinarello C. A., Saper C. B. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science. 1988 Apr 15;240(4850):321–324. doi: 10.1126/science.3258444. [DOI] [PubMed] [Google Scholar]
  7. Busbridge N. J., Dascombe M. J., Tilders F. J., van Oers J. W., Linton E. A., Rothwell N. J. Central activation of thermogenesis and fever by interleukin-1 beta and interleukin-1 alpha involves different mechanisms. Biochem Biophys Res Commun. 1989 Jul 31;162(2):591–596. doi: 10.1016/0006-291x(89)92351-6. [DOI] [PubMed] [Google Scholar]
  8. Buzzetti R., McLoughlin L., Lavender P. M., Clark A. J., Rees L. H. Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. J Clin Invest. 1989 Feb;83(2):733–737. doi: 10.1172/JCI113940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Böhme M. W., Becker K., Scherbaum W. A., Jirikowski G., Späth-Schwalbe E., Fehm H. L., Pfeiffer E. F. No expression of ir-ACTH on stimulated peripheral blood leukocytes. Horm Metab Res. 1987 Dec;19(12):670–671. doi: 10.1055/s-2007-1011908. [DOI] [PubMed] [Google Scholar]
  10. Dinarello C. A. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. doi: 10.1016/s0065-2776(08)60642-2. [DOI] [PubMed] [Google Scholar]
  11. Dunn A. J., Powell M. L., Gaskin J. M. Virus-induced increases in plasma corticosterone. Science. 1987 Dec 4;238(4832):1423–1425. doi: 10.1126/science.3685987. [DOI] [PubMed] [Google Scholar]
  12. Ferreira S. H., Lorenzetti B. B., Bristow A. F., Poole S. Interleukin-1 beta as a potent hyperalgesic agent antagonized by a tripeptide analogue. Nature. 1988 Aug 25;334(6184):698–700. doi: 10.1038/334698a0. [DOI] [PubMed] [Google Scholar]
  13. Gregory S. A., Kornbluth R. S., Helin H., Remold H. G., Edgington T. S. Monocyte procoagulant inducing factor: a lymphokine involved in the T cell-instructed monocyte procoagulant response to antigen. J Immunol. 1986 Nov 15;137(10):3231–3239. [PubMed] [Google Scholar]
  14. Halloran P. F., Urmson J., Van der Meide P. H., Autenried P. Regulation of MHC expression in vivo. II. IFN-alpha/beta inducers and recombinant IFN-alpha modulate MHC antigen expression in mouse tissues. J Immunol. 1989 Jun 15;142(12):4241–4247. [PubMed] [Google Scholar]
  15. Hopp T. P., Dower S. K., March C. J. The molecular forms of interleukin-1. Immunol Res. 1986;5(4):271–280. doi: 10.1007/BF02935500. [DOI] [PubMed] [Google Scholar]
  16. Johnson E. W., Blalock J. E., Smith E. M. ACTH receptor-mediated induction of leukocyte cyclic AMP. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1205–1211. doi: 10.1016/s0006-291x(88)81002-7. [DOI] [PubMed] [Google Scholar]
  17. Johnson H. M., Smith E. M., Torres B. A., Blalock J. E. Regulation of the in vitro antibody response by neuroendocrine hormones. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4171–4174. doi: 10.1073/pnas.79.13.4171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnson H. M., Torres B. A., Smith E. M., Dion L. D., Blalock J. E. Regulation of lymphokine (gamma-interferon) production by corticotropin. J Immunol. 1984 Jan;132(1):246–250. [PubMed] [Google Scholar]
  19. Karalis K., Sano H., Redwine J., Listwak S., Wilder R. L., Chrousos G. P. Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science. 1991 Oct 18;254(5030):421–423. doi: 10.1126/science.1925600. [DOI] [PubMed] [Google Scholar]
  20. Katsuura G., Gottschall P. E., Arimura A. Identification of a high-affinity receptor for interleukin-1 beta in rat brain. Biochem Biophys Res Commun. 1988 Oct 14;156(1):61–67. doi: 10.1016/s0006-291x(88)80805-2. [DOI] [PubMed] [Google Scholar]
  21. Katsuura G., Gottschall P. E., Dahl R. R., Arimura A. Adrenocorticotropin release induced by intracerebroventricular injection of recombinant human interleukin-1 in rats: possible involvement of prostaglandin. Endocrinology. 1988 May;122(5):1773–1779. doi: 10.1210/endo-122-5-1773. [DOI] [PubMed] [Google Scholar]
  22. Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., Jr Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. J Immunol. 1984 Sep;133(3):1339–1345. [PubMed] [Google Scholar]
  23. Koff W. C., Dunegan M. A. Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones. J Immunol. 1985 Jul;135(1):350–354. [PubMed] [Google Scholar]
  24. Lacaze-Masmonteil T., de Keyzer Y., Luton J. P., Kahn A., Bertagna X. Characterization of proopiomelanocortin transcripts in human nonpituitary tissues. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7261–7265. doi: 10.1073/pnas.84.20.7261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lolait S. J., Clements J. A., Markwick A. J., Cheng C., McNally M., Smith A. I., Funder J. W. Pro-opiomelanocortin messenger ribonucleic acid and posttranslational processing of beta endorphin in spleen macrophages. J Clin Invest. 1986 Jun;77(6):1776–1779. doi: 10.1172/JCI112501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lolait S. J., Lim A. T., Toh B. H., Funder J. W. Immunoreactive beta-endorphin in a subpopulation of mouse spleen macrophages. J Clin Invest. 1984 Jan;73(1):277–280. doi: 10.1172/JCI111203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Milenkovic L., Rettori V., Snyder G. D., Beutler B., McCann S. M. Cachectin alters anterior pituitary hormone release by a direct action in vitro. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2418–2422. doi: 10.1073/pnas.86.7.2418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Munn N. A., Lum L. G. Immunoregulatory effects of alpha-endorphin, beta-endorphin, methionine-enkephalin, and adrenocorticotropic hormone on anti-tetanus toxoid antibody synthesis by human lymphocytes. Clin Immunol Immunopathol. 1989 Sep;52(3):376–385. doi: 10.1016/0090-1229(89)90152-9. [DOI] [PubMed] [Google Scholar]
  29. Naitoh Y., Fukata J., Tominaga T., Nakai Y., Tamai S., Mori K., Imura H. Interleukin-6 stimulates the secretion of adrenocorticotropic hormone in conscious, freely-moving rats. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1459–1463. doi: 10.1016/s0006-291x(88)81305-6. [DOI] [PubMed] [Google Scholar]
  30. Olsen N. J., Nicholson W. E., DeBold C. R., Orth D. N. Lymphocyte-derived adrenocorticotropin is insufficient to stimulate adrenal steroidogenesis in hypophysectomized rats. Endocrinology. 1992 Apr;130(4):2113–2119. doi: 10.1210/endo.130.4.1312443. [DOI] [PubMed] [Google Scholar]
  31. Reder A. T., Pinamaneni S., Smyka W., Nutter D. ACTH production by human mononuclear cells. Ann N Y Acad Sci. 1988;540:589–591. doi: 10.1111/j.1749-6632.1988.tb27182.x. [DOI] [PubMed] [Google Scholar]
  32. Reder A., Birnbaum G. B-cell differentiation in multiple sclerosis and the effect of intravenous ACTH. Neurology. 1983 Apr;33(4):442–446. doi: 10.1212/wnl.33.4.442. [DOI] [PubMed] [Google Scholar]
  33. Sharp B. M., Matta S. G., Peterson P. K., Newton R., Chao C., Mcallen K. Tumor necrosis factor-alpha is a potent ACTH secretagogue: comparison to interleukin-1 beta. Endocrinology. 1989 Jun;124(6):3131–3133. doi: 10.1210/endo-124-6-3131. [DOI] [PubMed] [Google Scholar]
  34. Smith A. I., Funder J. W. Proopiomelanocortin processing in the pituitary, central nervous system, and peripheral tissues. Endocr Rev. 1988 Feb;9(1):159–179. doi: 10.1210/edrv-9-1-159. [DOI] [PubMed] [Google Scholar]
  35. Smith E. M., Galin F. S., LeBoeuf R. D., Coppenhaver D. H., Harbour D. V., Blalock J. E. Nucleotide and amino acid sequence of lymphocyte-derived corticotropin: endotoxin induction of a truncated peptide. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1057–1060. doi: 10.1073/pnas.87.3.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Smith E. M., Meyer W. J., Blalock J. E. Virus-induced corticosterone in hypophysectomized mice: a possible lymphoid adrenal axis. Science. 1982 Dec 24;218(4579):1311–1312. doi: 10.1126/science.6183748. [DOI] [PubMed] [Google Scholar]
  37. Smith E. M., Morrill A. C., Meyer W. J., 3rd, Blalock J. E. Corticotropin releasing factor induction of leukocyte-derived immunoreactive ACTH and endorphins. 1986 Jun 26-Jul 2Nature. 321(6073):881–882. doi: 10.1038/321881a0. [DOI] [PubMed] [Google Scholar]
  38. Smith L. R., Brown S. L., Blalock J. E. Interleukin-2 induction of ACTH secretion: presence of an interleukin-2 receptor alpha-chain-like molecule on pituitary cells. J Neuroimmunol. 1989 Feb;21(2-3):249–254. doi: 10.1016/0165-5728(89)90181-1. [DOI] [PubMed] [Google Scholar]
  39. Sobel D. O. Characterization of 12-O-tetradecanoyl-phorbol-13 acetate mediated ACTH release. Endocr Res. 1988;14(2-3):149–163. doi: 10.3109/07435808809032983. [DOI] [PubMed] [Google Scholar]
  40. Sobel D. O. Corticotropin releasing hormone and arginine vasopressin stimulation of ACTH and substance P in human mononuclear leukocytes. Endocr Res. 1990;16(2):283–292. doi: 10.1080/07435809009033006. [DOI] [PubMed] [Google Scholar]
  41. Uehara A., Gottschall P. E., Dahl R. R., Arimura A. Stimulation of ACTH release by human interleukin-1 beta, but not by interleukin-1 alpha, in conscious, freely-moving rats. Biochem Biophys Res Commun. 1987 Aug 14;146(3):1286–1290. doi: 10.1016/0006-291x(87)90788-1. [DOI] [PubMed] [Google Scholar]
  42. Webster E. L., Battaglia G., De Souza E. B. Functional corticotropin-releasing factor (CRF) receptors in mouse spleen: evidence from adenylate cyclase studies. Peptides. 1989 Mar-Apr;10(2):395–401. doi: 10.1016/0196-9781(89)90049-1. [DOI] [PubMed] [Google Scholar]
  43. Westly H. J., Kleiss A. J., Kelley K. W., Wong P. K., Yuen P. H. Newcastle disease virus-infected splenocytes express the proopiomelanocortin gene. J Exp Med. 1986 Jun 1;163(6):1589–1594. doi: 10.1084/jem.163.6.1589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Whitcomb R. W., Linehan W. M., Wahl L. M., Knazek R. A. Monocytes stimulate cortisol production by cultured human adrenocortical cells. J Clin Endocrinol Metab. 1988 Jan;66(1):33–38. doi: 10.1210/jcem-66-1-33. [DOI] [PubMed] [Google Scholar]

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