Skip to main content
SpringerLink
Log in

Differential regulation of soluble interleukin 1 release and membrane expression by pharmacologic agents

  • Inflammation and Immunomodulation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Membrane IL-1 (mIL-1) expression was compared with release of soluble IL-1 (sIL-1) by C3H/HeNCrl mouse peritoneal macrophages. Selective antagonists of protein kinase C (PKC) (H-7) and calmodulin (W-7) in combination inhibited LPS-induced mIL-1 and sIL-1 production, suggesting a role for these activation pathways in IL-1 induction. Low levels of A23187, when combined with OAG (a direct activator of PKC), stimulated mIL-1 expression in the absence of sIL-1 release. Induction of mIL-1 by LPS was inhibited by PGE2 and dibutyryl cAMP, but higher concentrations were required to inhibit mIL-1 expression compared with sIL-1 release. LTB4 alone did not induce mIL-1 or sIL-1 production. LTB4 did enhance LPS-induced mIL-1 expression but not sIL-1 release. These results indicate that mIL-1 expression and sIL-1 release are differentially regulated. Membrane IL-1 is induced by lower levels of certain stimuli and is less effectively inhibited than is sIL-1 release. This differential regulation is further evidence to support the existance of membrane IL-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J. J. Oppenheim, E. J. Kovacs, K. Matsushima and S. K. Durum,There is more than one interleukin 1. Immunol. Today7, 45–56 (1986).

    Article  Google Scholar 

  2. C. A. Dinarello,Interleukin 1. Rev. Infect. Dis.6, 51–95 (1984).

    PubMed  Google Scholar 

  3. P. W. Gray, D. Glaister, E. Chen, D. V. Goeddel and D. Pennica,Two interleukin 1 genes in the mouse: cloning and expression of the cDNA for murine interleukin 1β. J. Immunol.137, 3644–3648 (1986).

    PubMed  Google Scholar 

  4. C. J. March, B. Mosley, A. Larsen, D. P. Cerretti, G. Braedt, V. Price, S. Gillis, C. S. Henney, S. R. Kronheim, K. Grabtein, P. J. Conlon, T. P. Hopp and D. Cosman,Cloning, sequence and expression of two distinct human interleukin 1 complementary DNAs. Nature315, 641–647 (1985).

    Article  PubMed  Google Scholar 

  5. P. L. Kilian, K. Kaffka, A. S. Stern, D. Woehle, W. R. Benjamin, T. M. Dechiara, U. Gubler, J. J. Farrar, S. B. Mizel and P. T. Lomedico,Interleukin 1α and interleukin 1β bind to the same receptor on T cells. J. Immunol.136, 4509–4514 (1986).

    PubMed  Google Scholar 

  6. E. A. Rupp, P. M. Cameron, C. S. Ranawat, J. Schmidt and E. K. Bayne,Specific bioactivities of monocyte-derived interleukin 1α and interleukin 1β are similar to each other on cultured murine thymocytes and on cultured human connective tissue cells. J. Clin. Invest.78 836–839 (1986).

    PubMed  Google Scholar 

  7. P. T. Lomedico, U. Gubler, C. P. Hellmann, M. Dukovich, J. G. Giri, Y. E. Pan, K. Collier, R. Semionow, A. O. Chua and S. B. Mizel,Cloning and expression of murine interleukin 1 cDNA in Escherichia coli. Nature312, 458–462 (1984).

    Article  PubMed  Google Scholar 

  8. K. Matsushima, M. Taguchi, E. J. Kovacs, H. A. Young and J. J. Oppenheim,Intracellular localization of human monocyte associated interleukin 1 (IL-1) activity and release of biologically active IL-1 from monocytes by trypsin and plasmin. J. Immunol.136, 2883–2891 (1986).

    PubMed  Google Scholar 

  9. O. Bakouche, D. C. Brown and L. B. Lachman,Subcellular localization of human monocyte interleukin 1: evidence for an inactive precursor molecule and a possible mechanism for IL-1 release. J. Immunol.138, 4249–4255 (1987).

    PubMed  Google Scholar 

  10. D. Hazuda, J. C. Lee and P. R. Young,The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1α and interleukin 1β.J. Biol. Chem. 263, 8473–8479 (1988).

    PubMed  Google Scholar 

  11. Y. Kobayashi, E. Appella, M. Yamada, T. D. Copeland, J. J. Oppenheim and K. Matsushima,Phosphorylation of intracellular precursors of human IL-1. J. Immunol.140, 2279–2287 (1988).

    PubMed  Google Scholar 

  12. H. U. Beuscher and H. R. Colten,Structure and function of membrane IL-1. Mol. Immunol.25, 1189–1199 (1988).

    Article  PubMed  Google Scholar 

  13. E. A. Kurt-Jones, D. I. Beller, S. B. Mizel and E. R. Unanue,Identification of a membrane-associated interleukin 1 in macrophages.Proc. Natl. Acad. Sci. USA 82, 1204–1208 (1985).

    PubMed  Google Scholar 

  14. E. A. Kurt-Jones, H. W. Virgin IV and E. R. Unanue,Relationship of macrophage Ia and membrane IL-i expression to antigen presentation. J. Immunol.135, 3652–3654 (1985).

    PubMed  Google Scholar 

  15. E. A. Kurt-Jones, H. W. Virgin IV and E. R. Unanue,In vivo and in vitro expression of macrophage membrane interleukin 1 in response to soluble and particulate stimuli. J. Immunol.137, 10–14 (1986).

    PubMed  Google Scholar 

  16. C. T. Weaver and E. R. Unanue,T cell induction of membrane IL-1 on macrophages. J. Immunol.137, 3868–3873 (1986).

    PubMed  Google Scholar 

  17. P. J. Conlon, K. H. Grabstein, A. Alpert, K. S. Prickett, T. P. Hopp and S. Gillis,Localization of human mononuclear cell interleukin 1. J. Immunol.139, 98–102 (1987).

    PubMed  Google Scholar 

  18. E. A. Kurt-Jones, W. Fiers and J. S. Pober,Membrane interleukin 1 induction on human endothelial cells and dermal fibroblasts. J. Immunol.139, 2317–2324 (1987).

    PubMed  Google Scholar 

  19. R. C. Fuhlbrigge, K. C. Sheehan, R. D. Schreiber, D. D. Chaplin and E. R. Unanue,Monoclonal antibodies to murine IL 1α: production, characterization, and inhibition of membrane-associated IL-1 activity. J. Immunol.141, 2643–2650 (1988).

    PubMed  Google Scholar 

  20. H. U. Beuscher, R. J. Fallon and H. R. Colten,Macrophage membrane interleukin 1 regulates the expression of acute phase proteins in human hepatoma Hep 3B cells. J. Immunol.139, 1896–1901 (1987).

    PubMed  Google Scholar 

  21. L. L. Minnich-Carruth, J. Suttles, and S. B. Mizel,Evidence against the existance of a membrane form of murine IL-1α. J. Immunol.142, 526–530 (1989).

    PubMed  Google Scholar 

  22. S. L. Kunkel, S. W. Chensue and S. H. Phan,Prostaglandins as endogenous mediators of interleukin 1 production. J. Immunol.136, 186–192 (1986).

    PubMed  Google Scholar 

  23. S. R. Brandwein,Regulation of interleukin 1 production by mouse peritoneal macrophages: effects of arachidonic acid metabolites, cyclic nucleotides, and interferons. J. Biol. Chem.261, 8624–8632 (1986).

    PubMed  Google Scholar 

  24. P. J. Knudsen, C. A. Dinarello and T. B. Strom,Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J. Immunol.137, 3189–3194 (1986).

    PubMed  Google Scholar 

  25. D. S. Snyder and E. R. Unanue,Corticosteroids inhibit murine macrophage la expression and interleukin 1 production. J. Immunol.129, 1803–1805 (1982).

    PubMed  Google Scholar 

  26. S. W. Lee, A.-P. Tsou, H. Chan, J. Thomas, K. Petrie, E. M. Eugui and A. C. Allison,Glucocorticoids selectively inhibit the transcription of the interleukin 1β mRNA and decrease the stability of interleukin 1β mRNA. Proc. Natl. Acad. Sci. USA85, 1204–1208 (1988).

    PubMed  Google Scholar 

  27. K. Matsushima and J. J. Oppenheim,Calcium ionophore (A23187) increases interleukin 1 (IL-1) production by human peripheral blood monocytes and interacts synergistically with IL-1 to augment concanavalin A stimulated thymocyte proliferation. Cell. Immunol.90, 226–233 (1985).

    Article  PubMed  Google Scholar 

  28. H. Shinomiya and M. Nakano,Calcium ionophore A23187 does not stimulate lipopolysaccharide nonresponsive C3H/HeJ peritoneal macrophages to produce interleukin 1. J. Immunol.139, 2730–2736 (1987).

    PubMed  Google Scholar 

  29. M. Rola-Pleszcynski and I. Lemaire,Leukotrienes augment interleukin 1 production by monocytes.J. Immunol. 135, 3958–3961 (1985).

    PubMed  Google Scholar 

  30. D. Boraschi, S. Censini and A. Tagliabue,Interferon-reduces macrophage-suppressive activity by inhibiting prostaglandin E 2 release and inducing interleukin 1 production. J. Immunol.133, 764–768 (1984).

    PubMed  Google Scholar 

  31. E. P. Amento, J. T. Kurnick and S. M. Krane,Interleukin 1 production by the human monocyte cell line U937 requires a lymphokine signal distinct from interleukin 2 or interferons. J. Immunol.134, 350–357 (1985).

    PubMed  Google Scholar 

  32. P. Ghezzi and C. A. Dinarello,IL-1 induces IL-1. III. Specific inhibition of IL-1 production by IFN-γ. J. Immunol.140, 4238–4244 (1988).

    PubMed  Google Scholar 

  33. T. L. Gerrard, J. P. Siegel, D. R. Dyer and K. C. Zoon,Differential effects of interferon-α and interferon-γ on interleukin 1 secretion by monocytes. J. Immunol.138, 2535–2540 (1987).

    PubMed  Google Scholar 

  34. S. R. Brandwein, E. Skamene, J. Aubut, F. Gervais and M. N. Nesbitt,Genetic regulation of lipopolysaccharide-induced interleukin 1 production by murine peritoneal macrophages. J. Immunol.138, 4263–4269 (1987).

    PubMed  Google Scholar 

  35. M. M. Bradford,A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem.72, 248–254 (1976).

    PubMed  Google Scholar 

  36. W. E. C. Wacker, D. D. Ulmer and B. L. Vallee,metalloenzymes and myocardial infarction. II. Malic acid and lactic acid dehydrogenase activities and zinc concentrations in serum. N. Engl. J. Med.255, 449–456 (1956).

    Google Scholar 

  37. G. Lange-Wantzin, R. Rothlein, J. Kahn and R. B. Faanes,Effect of UV irradiation on expression of membrane IL-1 by rat macrophages. J. Immunol.138, 3803–3807 (1987).

    PubMed  Google Scholar 

  38. E. J. Kovacs, D. Radzioch, H. A. Young and L. Varesio,Differential inhibition of IL-1 and TNF-α mRNA expression by agents which block second messenger pathways in murine macrophages. J. Immunol.141, 3101–3105 (1988).

    PubMed  Google Scholar 

  39. I. G. Otterness, M. L. Bliven, J. D. Eskra, M. Reinke and D. C. Hanson,The pharmacologic regulation of interleukin 1 production: the role of prostaglandins. Cell. Immunol.114, 385–397 (1988).

    Article  PubMed  Google Scholar 

  40. L. M. Nagelkerken and P. J. C. Van Breda Vriesman,Membrane-associated IL-1-like activity on rat dendritic cells. J. Immunol.136, 2164–2170 (1986).

    PubMed  Google Scholar 

  41. H. Streck, C. Gunther, H. U. Beuscher and M. Rollinghoff,Studies on the release of cell-associated interleukin 1 by paraformaldehyde-treated murine macrophages. Eur. J. Immunol.18, 1609–1613 (1988).

    PubMed  Google Scholar 

  42. D. T. Brody and S. K. Durum,Membrane IL-1: IL-1α precursor binds to the plasma membrane via a lectin-like interaction. J. Immunol.143, 1183–1187 (1989).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatic Disease Unit, Montreal General Hospital Research Institute, McGill University, H3G 1A, Montreal, Quebec, Canada

    S. R. Brandwein

Authors
  1. S. R. Brandwein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brandwein, S.R. Differential regulation of soluble interleukin 1 release and membrane expression by pharmacologic agents. Agents and Actions 30, 381–392 (1990). https://doi.org/10.1007/BF01966303

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01966303

Keywords

Search

Navigation