The Journal of Immunology, Vol 138, Issue 5 1447-1456, Copyright © 1987 by American Association of Immunologists

ARTICLES

Studies on the molecular nature of human interleukin 1

PE Auron, SJ Warner, AC Webb, JG Cannon, HA Bernheim, KJ McAdam, LJ Rosenwasser, G LoPreste, SF Mucci and CA Dinarello

Adherent human blood monocytes were stimulated with heat-killed Staphylococcus albus or Escherichia coli lipopolysaccharide in the presence of 35S-methionine-, [3H]leucine-, or 14C-labeled amino acids. After incubation, interleukin 1 (IL 1) activity in the supernatant medium was purified over an anti-human IL 1 immunoadsorbent followed by gel filtration and chromatofocusing. The purity of the IL 1 was assessed by fluorography of one- and two-dimensional SDS-polyacrylamide gel electrophoresis. Isoelectric and chromatofocusing of low m.w. proteins (less than 20,000 m.w.) revealed three charged 18,000 m.w. species of IL 1 with approximate pI's of 7, 6, and 5, with the most abundant form at pI 7. During the purification procedures, lymphocyte co-mitogenic activity, fever in rabbits, and prostaglandin E2 release from dermal fibroblasts co-eluted in the same fractions. In addition, these fractions were active when injected into endotoxin-resistant C3H/HeJ mice for the production of fever, the induction of serum amyloid A protein, a decrease in serum iron concentration, and an increase in the number of circulating neutrophils. Fluorography revealed homogeneous bands with an m.w. of about 18,000 which correlated with these biological activities. The specific activity of the pI 6 or 5 IL 1, as judged by the ratio of T cell co-mitogenic activity to incorporated radiolabeled amino acid, was at least 10-fold greater than that observed for the pI 7 form. This result suggests that the amino acid compositions of the two 18,000 m.w. acidic forms are unrelated to the pI 7 species. These results also demonstrate that the pI 7 human monocyte IL 1 is the predominant 18,000 m.w. form synthesized and, furthermore, that homogeneous pI 7 IL 1 exhibits multiple biological properties on various tissues by modulating immunologic, inflammatory, metabolic, and neurologic functions. Data are also presented for the existence of a high m.w. (32,000) human pro- IL 1 molecule as the predominant monocytic intracellular form. This pro- IL 1 is degraded artifactually during isolation to lower m.w. forms in the presence of an extracellular serine protease activity. These data are consistent with a model for IL 1 secretion in which pro-IL 1 is first synthesized within the cell and is processed during or after extracellular transport.

This article has been cited by other articles:

				R. Backhaus, C. Zehe, S. Wegehingel, A. Kehlenbach, B. Schwappach, and W. Nickel Unconventional protein secretion: membrane translocation of FGF-2 does not require protein unfolding J. Cell Sci., May 1, 2004; 117(9): 1727 - 1736. [Abstract] [Full Text] [PDF]

				T. Schafer, H. Zentgraf, C. Zehe, B. Brugger, J. Bernhagen, and W. Nickel Unconventional Secretion of Fibroblast Growth Factor 2 Is Mediated by Direct Translocation across the Plasma Membrane of Mammalian Cells J. Biol. Chem., February 20, 2004; 279(8): 6244 - 6251. [Abstract] [Full Text] [PDF]

				J. Yang, W. C. Hooper, D. J. Phillips, and D. F. Talkington Regulation of Proinflammatory Cytokines in Human Lung Epithelial Cells Infected with Mycoplasma pneumoniae Infect. Immun., July 1, 2002; 70(7): 3649 - 3655. [Abstract] [Full Text] [PDF]

				L. R. Leon Molecular Biology of Thermoregulation: Invited Review: Cytokine regulation of fever: studies using gene knockout mice J Appl Physiol, June 1, 2002; 92(6): 2648 - 2655. [Abstract] [Full Text] [PDF]

				D. G. Perregaux, K. Bhavsar, L. Contillo, J. Shi, and C. A. Gabel Antimicrobial Peptides Initiate IL-1{beta} Posttranslational Processing: A Novel Role Beyond Innate Immunity J. Immunol., March 15, 2002; 168(6): 3024 - 3032. [Abstract] [Full Text] [PDF]

				K. Shida, I. Shiratori, M. Matsumoto, Y. Fukumori, A. Matsuhisa, S. Kikkawa, S. Tsuji, H. Okamura, K. Toyoshima, and T. Seya An Alternative Form of IL-18 in Human Blood Plasma: Complex Formation with IgM Defined by Monoclonal Antibodies J. Immunol., June 1, 2001; 166(11): 6671 - 6679. [Abstract] [Full Text] [PDF]

				D. Cerretti, C. Kozlosky, B Mosley, N Nelson, K Van Ness, T. Greenstreet, C. March, Kronheim SR, T Druck, L. Cannizzaro, et al. Molecular cloning of the interleukin-1 beta converting enzyme Science, April 3, 1992; 256(5053): 97 - 100. [Abstract] [PDF]

				B Ensoli, S Nakamura, S. Salahuddin, P Biberfeld, L Larsson, B Beaver, F Wong-Staal, and R. Gallo AIDS-Kaposi's sarcoma-derived cells express cytokines with autocrine and paracrine growth effects Science, January 13, 1989; 243(4888): 223 - 226. [Abstract] [PDF]