Abstract
Interleukin-1 (IL-1) is known to synergize with phorbol esters in the induction of interleukin-2 (IL-2) expression in T-lymphoid leukemia cells and proliferation of mouse thymocytes. We used a plasmid construct containing the bacterial gene for chloramphenicol acetyltransferase under the control of the human IL-2 promoter to study the nature of this synergism in the murine thymoma cell line EL4. Although IL-1 induction of the IL-2 promoter in these cells required costimulus with phorbol myristate acetate, the signal induced by IL-1 was qualitatively different. We provide evidence to support the hypothesis that the phorbol ester signal is mediated by protein kinase C, and we show that the IL-1 signal is not. That IL-1 and phorbol myristate acetate represent different stimuli was shown by their response to protein kinase C inhibitors, capacity to synergize with increased intracellular free calcium, and requirement for protein synthesis. In addition we show that pretreatment with IL-1 can prime EL4 cells to subsequent activation by concentrations of phorbol esters not normally sufficient to induce IL-2 expression. Pretreated cells remained primed for at least 40 h after removal of the IL-1. Neither phorbol myristate acetate nor a calcium ionophore was capable of preactivating EL4 cells.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abraham R. T., Ho S. N., Barna T. J., McKean D. J. Transmembrane signaling during interleukin 1-dependent T cell activation. Interactions of signal 1- and signal 2-type mediators with the phosphoinositide-dependent signal transduction mechanism. J Biol Chem. 1987 Feb 25;262(6):2719–2728. [PubMed] [Google Scholar]
- Alton N. K., Vapnek D. Nucleotide sequence analysis of the chloramphenicol resistance transposon Tn9. Nature. 1979 Dec 20;282(5741):864–869. doi: 10.1038/282864a0. [DOI] [PubMed] [Google Scholar]
- Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
- Bagby G. C., Jr, Dinarello C. A., Wallace P., Wagner C., Hefeneider S., McCall E. Interleukin 1 stimulates granulocyte macrophage colony-stimulating activity release by vascular endothelial cells. J Clin Invest. 1986 Nov;78(5):1316–1323. doi: 10.1172/JCI112717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
- Berridge M. J. Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem. 1987;56:159–193. doi: 10.1146/annurev.bi.56.070187.001111. [DOI] [PubMed] [Google Scholar]
- Boraschi D., Volpini G., Villa L., Nencioni L., Scapigliati G., Nucci D., Antoni G., Matteucci G., Cioli F., Tagliabue A. A monoclonal antibody to the IL-1 beta peptide 163-171 blocks adjuvanticity but not pyrogenicity of IL-1 beta in vivo. J Immunol. 1989 Jul 1;143(1):131–134. [PubMed] [Google Scholar]
- Casagli M. C., Borri M. G., D'Ettorre C., Galeotti C. L., Di Liegro C., Ghiara P., Antoni G. Use of ZetaPrep cartridge for the purification of human recombinant interleukin 1 beta. Prep Biochem. 1989;19(1):23–35. doi: 10.1080/10826068908544894. [DOI] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
- Crabtree G. R. Contingent genetic regulatory events in T lymphocyte activation. Science. 1989 Jan 20;243(4889):355–361. doi: 10.1126/science.2783497. [DOI] [PubMed] [Google Scholar]
- Crooke S. T., Mattern M., Sarau H. M., Winkler J. D., Balcarek J., Wong A., Bennett C. F. The signal transduction system of the leukotriene D4 receptor. Trends Pharmacol Sci. 1989 Mar;10(3):103–107. doi: 10.1016/0165-6147(89)90206-x. [DOI] [PubMed] [Google Scholar]
- Dente L., Cesareni G., Cortese R. pEMBL: a new family of single stranded plasmids. Nucleic Acids Res. 1983 Mar 25;11(6):1645–1655. doi: 10.1093/nar/11.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
- Fujita T., Shibuya H., Ohashi T., Yamanishi K., Taniguchi T. Regulation of human interleukin-2 gene: functional DNA sequences in the 5' flanking region for the gene expression in activated T lymphocytes. Cell. 1986 Aug 1;46(3):401–405. doi: 10.1016/0092-8674(86)90660-4. [DOI] [PubMed] [Google Scholar]
- Fujita T., Takaoka C., Matsui H., Taniguchi T. Structure of the human interleukin 2 gene. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7437–7441. doi: 10.1073/pnas.80.24.7437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hannun Y. A., Bell R. M. Lysosphingolipids inhibit protein kinase C: implications for the sphingolipidoses. Science. 1987 Feb 6;235(4789):670–674. doi: 10.1126/science.3101176. [DOI] [PubMed] [Google Scholar]
- Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
- Hilfiker M. L., Moore R. N., Farrar J. J. Biologic properties of chromatographically separated murine thymoma-derived Interleukin 2 and colony-stimulating factor. J Immunol. 1981 Nov;127(5):1983–1987. [PubMed] [Google Scholar]
- Huang F. L., Yoshida Y., Cunha-Melo J. R., Beaven M. A., Huang K. P. Differential down-regulation of protein kinase C isozymes. J Biol Chem. 1989 Mar 5;264(7):4238–4243. [PubMed] [Google Scholar]
- Jefferson A. B., Schulman H. Sphingosine inhibits calmodulin-dependent enzymes. J Biol Chem. 1988 Oct 25;263(30):15241–15244. [PubMed] [Google Scholar]
- Larsson E. L., Iscove N. N., Coutinho A. Two distinct factors are required for induction of T-cell growth. Nature. 1980 Feb 14;283(5748):664–666. doi: 10.1038/283664a0. [DOI] [PubMed] [Google Scholar]
- Lowenthal J. W., Cerottini J. C., MacDonald H. R. Interleukin 1-dependent induction of both interleukin 2 secretion and interleukin 2 receptor expression by thymoma cells. J Immunol. 1986 Aug 15;137(4):1226–1231. [PubMed] [Google Scholar]
- Matsushima K., Yodoi J., Tagaya Y., Oppenheim J. J. Down-regulation of interleukin 1 (IL 1) receptor expression by IL 1 and fate of internalized 125I-labeled IL 1 beta in a human large granular lymphocyte cell line. J Immunol. 1986 Nov 15;137(10):3183–3188. [PubMed] [Google Scholar]
- Mizel S. B., Kilian P. L., Lewis J. C., Paganelli K. A., Chizzonite R. A. The interleukin 1 receptor. Dynamics of interleukin 1 binding and internalization in T cells and fibroblasts. J Immunol. 1987 May 1;138(9):2906–2912. [PubMed] [Google Scholar]
- Muegge K., Williams T. M., Kant J., Karin M., Chiu R., Schmidt A., Siebenlist U., Young H. A., Durum S. K. Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1. Science. 1989 Oct 13;246(4927):249–251. doi: 10.1126/science.2799385. [DOI] [PubMed] [Google Scholar]
- Mukaida N., Kasahara T., Yagisawa H., Shioiri-Nakano K., Kawai T. Signal requirement for interleukin-1-dependent interleukin 2 production by a human leukemia-derived HSB.2 subclone. J Immunol. 1987 Nov 15;139(10):3321–3329. [PubMed] [Google Scholar]
- Neer E. J., Clapham D. E. Roles of G protein subunits in transmembrane signalling. Nature. 1988 May 12;333(6169):129–134. doi: 10.1038/333129a0. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
- Oettgen H. C., Terhorst C., Cantley L. C., Rosoff P. M. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985 Mar;40(3):583–590. doi: 10.1016/0092-8674(85)90206-5. [DOI] [PubMed] [Google Scholar]
- Parker J., Daniel L. W., Waite M. Evidence of protein kinase C involvement in phorbol diester-stimulated arachidonic acid release and prostaglandin synthesis. J Biol Chem. 1987 Apr 15;262(11):5385–5393. [PubMed] [Google Scholar]
- Pressman B. C. Biological applications of ionophores. Annu Rev Biochem. 1976;45:501–530. doi: 10.1146/annurev.bi.45.070176.002441. [DOI] [PubMed] [Google Scholar]
- Rosoff P. M., Savage N., Dinarello C. A. Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism. Cell. 1988 Jul 1;54(1):73–81. doi: 10.1016/0092-8674(88)90181-x. [DOI] [PubMed] [Google Scholar]
- Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26;47(6):921–928. doi: 10.1016/0092-8674(86)90807-x. [DOI] [PubMed] [Google Scholar]
- Shirakawa F., Chedid M., Suttles J., Pollok B. A., Mizel S. B. Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein. Mol Cell Biol. 1989 Mar;9(3):959–964. doi: 10.1128/mcb.9.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shirakawa F., Yamashita U., Chedid M., Mizel S. B. Cyclic AMP--an intracellular second messenger for interleukin 1. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8201–8205. doi: 10.1073/pnas.85.21.8201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siebenlist U., Durand D. B., Bressler P., Holbrook N. J., Norris C. A., Kamoun M., Kant J. A., Crabtree G. R. Promoter region of interleukin-2 gene undergoes chromatin structure changes and confers inducibility on chloramphenicol acetyltransferase gene during activation of T cells. Mol Cell Biol. 1986 Sep;6(9):3042–3049. doi: 10.1128/mcb.6.9.3042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simon P. L. Calcium mediates one of the signals required for interleukin 1 and 2 production by murine cell lines. Cell Immunol. 1984 Sep;87(2):720–726. doi: 10.1016/0008-8749(84)90042-x. [DOI] [PubMed] [Google Scholar]
- Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanton T. H., Maynard M., Bomsztyk K. Effect of interleukin-1 on intracellular concentration of sodium, calcium, and potassium in 70Z/3 cells. J Biol Chem. 1986 May 5;261(13):5699–5701. [PubMed] [Google Scholar]
- Svensson C., Akusjärvi G. Adenovirus VA RNAI mediates a translational stimulation which is not restricted to the viral mRNAs. EMBO J. 1985 Apr;4(4):957–964. doi: 10.1002/j.1460-2075.1985.tb03724.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Damme J., Opdenakker G., Simpson R. J., Rubira M. R., Cayphas S., Vink A., Billiau A., Van Snick J. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med. 1987 Mar 1;165(3):914–919. doi: 10.1084/jem.165.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yokota T., Arai N., Lee F., Rennick D., Mosmann T., Arai K. Use of a cDNA expression vector for isolation of mouse interleukin 2 cDNA clones: expression of T-cell growth-factor activity after transfection of monkey cells. Proc Natl Acad Sci U S A. 1985 Jan;82(1):68–72. doi: 10.1073/pnas.82.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zucali J. R., Dinarello C. A., Oblon D. J., Gross M. A., Anderson L., Weiner R. S. Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest. 1986 Jun;77(6):1857–1863. doi: 10.1172/JCI112512. [DOI] [PMC free article] [PubMed] [Google Scholar]