Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Nov 1;168(5):1767–1779. doi: 10.1084/jem.168.5.1767

A human urine-derived interleukin 1 inhibitor. Homology with deoxyribonuclease I

PMCID: PMC2189114  PMID: 3263467

Abstract

We have previously reported that the urine of febrile humans contained large quantities of an inhibitor of IL-1-induced murine thymocyte proliferation that was a glycoprotein between 30 and 40 kD in size. In the present study this factor has been purified to homogeneity using a sequence of eight purification steps (ammonium sulfate precipitation, ion exchange chromatography, molecular sieve chromatography, hydrophobic affinity chromatography, hydroxylapatite chromatography, fast protein liquid chromatography, and two HPLC steps). SDS-PAGE analysis indicates that the purified material is a 38-kD molecule. Evidence based on a partial amino acid sequence analysis as well as enzyme studies indicates that this inhibitor is a type of human DNase I.

Full Text

The Full Text of this article is available as a PDF (919.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balavoine J. F., de Rochemonteix B., Williamson K., Seckinger P., Cruchaud A., Dayer J. M. Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s). J Clin Invest. 1986 Oct;78(4):1120–1124. doi: 10.1172/JCI112669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barak V., Treves A. J., Yanai P., Halperin M., Wasserman D., Biran S., Braun S. Interleukin 1 inhibitory activity secreted by a human myelomonocytic cell line (M20). Eur J Immunol. 1986 Nov;16(11):1449–1452. doi: 10.1002/eji.1830161122. [DOI] [PubMed] [Google Scholar]
  3. Berman M. A., Sandborg C. I., Calabia B. S., Andrews B. S., Friou G. J. Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS). Clin Immunol Immunopathol. 1987 Jan;42(1):133–140. doi: 10.1016/0090-1229(87)90180-2. [DOI] [PubMed] [Google Scholar]
  4. Brown K. M., Muchmore A. V., Rosenstreich D. L. Uromodulin, an immunosuppressive protein derived from pregnancy urine, is an inhibitor of interleukin 1. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9119–9123. doi: 10.1073/pnas.83.23.9119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown K. M., Rosenstreich D. L. Mechanism of action of a human interleukin 1 inhibitor. Cell Immunol. 1987 Mar;105(1):45–53. doi: 10.1016/0008-8749(87)90054-2. [DOI] [PubMed] [Google Scholar]
  6. Dinarello C. A. Biology of interleukin 1. FASEB J. 1988 Feb;2(2):108–115. [PubMed] [Google Scholar]
  7. Fujiwara H., Ellner J. J. Spontaneous production of a suppressor factor by the human macrophage-like cell line U937. I. Suppression of interleukin 1, interleukin 2, and mitogen-induced blastogenesis in mouse thymocytes. J Immunol. 1986 Jan;136(1):181–185. [PubMed] [Google Scholar]
  8. Hession C., Decker J. M., Sherblom A. P., Kumar S., Yue C. C., Mattaliano R. J., Tizard R., Kawashima E., Schmeissner U., Heletky S. Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. Science. 1987 Sep 18;237(4821):1479–1484. doi: 10.1126/science.3498215. [DOI] [PubMed] [Google Scholar]
  9. Kimball E. S., Pickeral S. F., Oppenheim J. J., Rossio J. L. Interleukin 1 activity in normal human urine. J Immunol. 1984 Jul;133(1):256–260. [PubMed] [Google Scholar]
  10. Kleinerman E. S., Lachman L. B., Knowles R. D., Snyderman R., Cianciolo G. J. A synthetic peptide homologous to the envelope proteins of retroviruses inhibits monocyte-mediated killing by inactivating interleukin 1. J Immunol. 1987 Oct 1;139(7):2329–2337. [PubMed] [Google Scholar]
  11. Korn J. H., Brown K. M., Downie E., Liao Z. H., Rosenstreich D. L. Augmentation of IL 1-induced fibroblast PGE2 production by a urine-derived IL 1 inhibitor. J Immunol. 1987 May 15;138(10):3290–3294. [PubMed] [Google Scholar]
  12. Lacks S. A. Deoxyribonuclease I in mammalian tissues. Specificity of inhibition by actin. J Biol Chem. 1981 Mar 25;256(6):2644–2648. [PubMed] [Google Scholar]
  13. Liao Z., Grimshaw R. S., Rosenstreich D. L. Identification of a specific interleukin 1 inhibitor in the urine of febrile patients. J Exp Med. 1984 Jan 1;159(1):126–136. doi: 10.1084/jem.159.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Liao Z., Haimovitz A., Chen Y., Chan J., Rosenstreich D. L. Characterization of a human interleukin 1 inhibitor. J Immunol. 1985 Jun;134(6):3882–3886. [PubMed] [Google Scholar]
  15. Lottspeich F. Identification of the phenylthiohydantoin derivatives of amino acids by high pressure liquid chromatography, using a ternary, isocratic solvent system. Hoppe Seylers Z Physiol Chem. 1980 Dec;361(12):1829–1834. doi: 10.1515/bchm2.1980.361.2.1829. [DOI] [PubMed] [Google Scholar]
  16. Muchmore A. V., Decker J. M. Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women. Science. 1985 Aug 2;229(4712):479–481. doi: 10.1126/science.2409603. [DOI] [PubMed] [Google Scholar]
  17. Muchmore A. V., Shifrin S., Decker J. M. In vitro evidence that carbohydrate moieties derived from uromodulin, an 85,000 dalton immunosuppressive glycoprotein isolated from human pregnancy urine, are immunosuppressive in the absence of intact protein. J Immunol. 1987 Apr 15;138(8):2547–2553. [PubMed] [Google Scholar]
  18. Ochs D. Protein contaminants of sodium dodecyl sulfate-polyacrylamide gels. Anal Biochem. 1983 Dec;135(2):470–474. doi: 10.1016/0003-2697(83)90714-5. [DOI] [PubMed] [Google Scholar]
  19. Paudel H. K., Liao T. H. Comparison of the three primary structures of deoxyribonuclease isolated from bovine, ovine, and porcine pancreas. Derivation of the amino acid sequence of ovine DNase and revision of the previously published amino acid sequence of bovine DNase. J Biol Chem. 1986 Dec 5;261(34):16012–16017. [PubMed] [Google Scholar]
  20. Roberts N. J., Jr, Prill A. H., Mann T. N. Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity. J Exp Med. 1986 Mar 1;163(3):511–519. doi: 10.1084/jem.163.3.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rodgers B. C., Scott D. M., Mundin J., Sissons J. G. Monocyte-derived inhibitor of interleukin 1 induced by human cytomegalovirus. J Virol. 1985 Sep;55(3):527–532. doi: 10.1128/jvi.55.3.527-532.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sandborg C. I., Berman M. A., Andrews B. S., Mirick G. R., Friou G. J. Increased production of an interleukin 1 (IL-1) inhibitor with fibroblast stimulating activity by mononuclear cells from patients with scleroderma. Clin Exp Immunol. 1986 Nov;66(2):312–319. [PMC free article] [PubMed] [Google Scholar]
  23. Scala G., Kuang Y. D., Hall R. E., Muchmore A. V., Oppenheim J. J. Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line. J Exp Med. 1984 Jun 1;159(6):1637–1652. doi: 10.1084/jem.159.6.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schwarz T., Urbanska A., Gschnait F., Luger T. A. UV-irradiated epidermal cells produce a specific inhibitor of interleukin 1 activity. J Immunol. 1987 Mar 1;138(5):1457–1463. [PubMed] [Google Scholar]
  25. Seckinger P., Lowenthal J. W., Williamson K., Dayer J. M., MacDonald H. R. A urine inhibitor of interleukin 1 activity that blocks ligand binding. J Immunol. 1987 Sep 1;139(5):1546–1549. [PubMed] [Google Scholar]
  26. Shou L., Schwartz S. A., Good R. A., Peng R., Chen C. L. A human soluble suppressor factor affecting lymphocyte responses in vitro. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6096–6100. doi: 10.1073/pnas.77.10.6096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tiku K., Tiku M. L., Liu S., Skosey J. L. Normal human neutrophils are a source of a specific interleukin 1 inhibitor. J Immunol. 1986 May 15;136(10):3686–3692. [PubMed] [Google Scholar]
  28. Zhang C. X., Decaussin G., de Turenne Tessier M., Daillie J., Ooka T. Identification of an Epstein-Barr virus-specific desoxyribonuclease gene using complementary DNA. Nucleic Acids Res. 1987 Mar 25;15(6):2707–2717. doi: 10.1093/nar/15.6.2707. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES