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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 May 1;88(9):3681–3685. doi: 10.1073/pnas.88.9.3681

cDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium.

S Haskill 1, G Martin 1, L Van Le 1, J Morris 1, A Peace 1, C F Bigler 1, G J Jaffe 1, C Hammerberg 1, S A Sporn 1, S Fong 1, et al.
PMCID: PMC51516  PMID: 1827201

Abstract

A cDNA encoding a receptor antagonist of interleukin 1 (IL-1ra), secreted from human monocytes, has recently been isolated and sequenced [Eisenberg, S. P., Evans, R. J., Arend, W. P., Verderber, E., Brewer, M. T., Hannum, C. H. & Thompson, R. C. (1990) Nature (London) 343, 341-346]. We have identified another version of this IL-1ra, which is predominantly expressed in epithelial cells. This IL-1ra lacks a leader sequence and, thus, is probably intracellular. Both proteins are derived from the same gene through use of an alternative transcriptional start site and internal splice-acceptor site. Expression of intracellular IL-1ra cDNA in COS cells demonstrated that the intracellular product specifically inhibited exogenous interleukin 1-dependent responses. Keratinocytes were shown to contain significant amounts of nonsecreted IL-1ra protein. Constitutive expression of the intracellular IL-1ra may be an intracellular defensive mechanism in exposed epithelial cells and/or may serve to regulate autocrine interleukin 1-mediated pathways of differentiation.

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Selected References

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  1. Acland P., Dixon M., Peters G., Dickson C. Subcellular fate of the int-2 oncoprotein is determined by choice of initiation codon. Nature. 1990 Feb 15;343(6259):662–665. doi: 10.1038/343662a0. [DOI] [PubMed] [Google Scholar]
  2. Arend W. P., Dayer J. M. Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis. Arthritis Rheum. 1990 Mar;33(3):305–315. doi: 10.1002/art.1780330302. [DOI] [PubMed] [Google Scholar]
  3. Arend W. P., Joslin F. G., Thompson R. C., Hannum C. H. An IL-1 inhibitor from human monocytes. Production and characterization of biologic properties. J Immunol. 1989 Sep 15;143(6):1851–1858. [PubMed] [Google Scholar]
  4. Carlson M., Botstein D. Two differentially regulated mRNAs with different 5' ends encode secreted with intracellular forms of yeast invertase. Cell. 1982 Jan;28(1):145–154. doi: 10.1016/0092-8674(82)90384-1. [DOI] [PubMed] [Google Scholar]
  5. Carter D. B., Deibel M. R., Jr, Dunn C. J., Tomich C. S., Laborde A. L., Slightom J. L., Berger A. E., Bienkowski M. J., Sun F. F., McEwan R. N. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Nature. 1990 Apr 12;344(6267):633–638. doi: 10.1038/344633a0. [DOI] [PubMed] [Google Scholar]
  6. Cooper K. D., Hammerberg C., Baadsgaard O., Elder J. T., Chan L. S., Sauder D. N., Voorhees J. J., Fisher G. IL-1 activity is reduced in psoriatic skin. Decreased IL-1 alpha and increased nonfunctional IL-1 beta. J Immunol. 1990 Jun 15;144(12):4593–4603. [PubMed] [Google Scholar]
  7. Curtis B. M., Widmer M. B., deRoos P., Qwarnstrom E. E. IL-1 and its receptor are translocated to the nucleus. J Immunol. 1990 Feb 15;144(4):1295–1303. [PubMed] [Google Scholar]
  8. 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]
  9. Eierman D. F., Johnson C. E., Haskill J. S. Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates. J Immunol. 1989 Mar 15;142(6):1970–1976. [PubMed] [Google Scholar]
  10. Eisenberg S. P., Evans R. J., Arend W. P., Verderber E., Brewer M. T., Hannum C. H., Thompson R. C. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990 Jan 25;343(6256):341–346. doi: 10.1038/343341a0. [DOI] [PubMed] [Google Scholar]
  11. Gillis S., Mizel S. B. T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1133–1137. doi: 10.1073/pnas.78.2.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grenfell S., Smithers N., Miller K., Solari R. Receptor-mediated endocytosis and nuclear transport of human interleukin 1 alpha. Biochem J. 1989 Dec 15;264(3):813–822. doi: 10.1042/bj2640813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hannum C. H., Wilcox C. J., Arend W. P., Joslin F. G., Dripps D. J., Heimdal P. L., Armes L. G., Sommer A., Eisenberg S. P., Thompson R. C. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990 Jan 25;343(6256):336–340. doi: 10.1038/343336a0. [DOI] [PubMed] [Google Scholar]
  14. Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
  15. Kupper T. S., Chua A. O., Flood P., McGuire J., Gubler U. Interleukin 1 gene expression in cultured human keratinocytes is augmented by ultraviolet irradiation. J Clin Invest. 1987 Aug;80(2):430–436. doi: 10.1172/JCI113090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maier J. A., Voulalas P., Roeder D., Maciag T. Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. Science. 1990 Sep 28;249(4976):1570–1574. doi: 10.1126/science.2218499. [DOI] [PubMed] [Google Scholar]
  17. Mosley B., Urdal D. L., Prickett K. S., Larsen A., Cosman D., Conlon P. J., Gillis S., Dower S. K. The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. J Biol Chem. 1987 Mar 5;262(7):2941–2944. [PubMed] [Google Scholar]
  18. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perlman D., Halvorson H. O., Cannon L. E. Presecretory and cytoplasmic invertase polypeptides encoded by distinct mRNAs derived from the same structural gene differ by a signal sequence. Proc Natl Acad Sci U S A. 1982 Feb;79(3):781–785. doi: 10.1073/pnas.79.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Qwarnstrom E. E., Page R. C., Gillis S., Dower S. K. Binding, internalization, and intracellular localization of interleukin-1 beta in human diploid fibroblasts. J Biol Chem. 1988 Jun 15;263(17):8261–8269. [PubMed] [Google Scholar]
  21. Ristow H. J. A major factor contributing to epidermal proliferation in inflammatory skin diseases appears to be interleukin 1 or a related protein. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1940–1944. doi: 10.1073/pnas.84.7.1940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sauder D. N., Stanulis-Praeger B. M., Gilchrest B. A. Autocrine growth stimulation of human keratinocytes by epidermal cell-derived thymocyte-activating factor: implications for skin aging. Arch Dermatol Res. 1988;280(2):71–76. doi: 10.1007/BF00417707. [DOI] [PubMed] [Google Scholar]
  24. Sporn S. A., Eierman D. F., Johnson C. E., Morris J., Martin G., Ladner M., Haskill S. Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. J Immunol. 1990 Jun 1;144(11):4434–4441. [PubMed] [Google Scholar]
  25. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]

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