Hostname: page-component-77c89778f8-vpsfw Total loading time: 0 Render date: 2024-07-16T13:10:37.569Z Has data issue: false hasContentIssue false
  • English
  • Français

Ex vivo evidence for PGE2 and LTB4 involvement in cutaneous leishmaniasis: relation with infection status and cytokine production

Published online by Cambridge University Press:  06 April 2009

S. Milano ,
F. Arcoleo ,
M. Dieli ,
R. D'agostino ,
G. De Nucci ,
P. D'agostino  and
E. Cillari
S. Milano
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
F. Arcoleo
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
M. Dieli
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
R. D'agostino
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
G. De Nucci
Affiliation:
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, PO Box 6111, 13081 Campinas, S.P., Brasil
P. D'agostino
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
E. Cillari
Affiliation:
Institute of General Pathology, University of Palermo, 211 Corso Tukory, 90134 Palermo, Italy
Get access Rights & Permissions [Opens in a new window]

Summary

Ex vivo culture of spleen cells from BALB/c mice infected with 2 × 106Leishmania major (L.major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2 (PGE2) and for leukotriene B4 (LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected against L. major by sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2 that were responsible for the depression of interferon-γ (IFN-γ) and tumour necrosis factor-α (TNFα) Th1-associated cytokines and for the relative increase in the interleukin-4 (IL-4) became higher and higher as the lesion progressed. On the contrary, the cured mice produced levels of PGE2 similar to normal uninfected controls, high levels of TNFα and IFN-γ and low levels of IL-4. Elevated levels of LTB4 were detected in the early stage of infection in the unprotected mice compared to cured ones, a sign of more intense inflammation and a stimulus for the recruitment of inflammatory cells. The observation that exogenous LTB4 was able to enhance in vitro both Th1 cytokines in cured mice and Th2 cytokines in unprotected ones suggests that LTB4 could act in the recruitment of the T cells already committed to Th1 or Th2 phenotype.

Keywords

Leishmania majorTNFαIFN-γPGE2LTB4
Type
Research Article
Information
Parasitology , Volume 112 , Issue 1 , January 1996 , pp. 13 - 19
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Akahoshi, T., Oppenheim, J. J. & Matsushima, K. (1988). Interleukin-1 stimulates its own receptor expression on human fibroblast through the endogenous production of prostaglandin(s). Journal of Clinical Investigation 82, 1219–24.CrossRefGoogle ScholarPubMed
Arcoleo, F., Milano, S., D'agostino, P. & Cillari, E. (1995). Effect of exogenous leukotriene B4 (LTB4) on BALB/c mice splenocyte production of Th1 and Th2lymphokines. International Journal of Immunopharmacology 17, 457–63.CrossRefGoogle Scholar
Betz, M. & Fox, B. S. (1991). Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. Journal of Immunology 146, 108–13.CrossRefGoogle Scholar
Bloom, B. R., Salgame, P. & Diamond, B. (1992). Revisiting and revising suppressor T cells. Immunology Today 13, 131–5.CrossRefGoogle ScholarPubMed
Bradley, D. J. (1977). Regulation of Leishmania populations within the host. II. Genetic control of acute susceptibility of mice to Leishmania donovani infection. Clinical and Experimental Immunology 30, 130–40.Google ScholarPubMed
Chouaib, S., Chatennoud, L., Klatmann, D. & Fradelizi, D. (1984). Mechanism of inhibition of human IL-2 production: PGE2 induction of suppressor T lymphocytes. Journal of Immunology 132, 1851–7.CrossRefGoogle ScholarPubMed
Cillari, E., Dieli, M., Maltese, E., Milano, S., Salerno, A. & Liew, F. Y. (1989). Enhancement of macrophage IL-1 production by Leishmania major infection in vitro and its inhibition by IFN-γ. Journal of Immunology 143, 2001–5.CrossRefGoogle ScholarPubMed
Cillari, E., Liew, F. Y. & Lelchuck, R. (1986). Suppression of interleukin-2 production by macrophages in susceptible BALB/c mice infected with Leishmania major. Infection and Immunity 54, 386–94.CrossRefGoogle ScholarPubMed
Cunha, F. Q., Moncada, S. & Liew, F. Y. (1992). Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-γ in murine macrophages. Biochemical and Biophysical Research Communications 182, 1155–9.CrossRefGoogle ScholarPubMed
De Nucci, G., Salmon, J. A. & Moncada, S. (1986). The synthesis of eicosanoids induced by anaphylaxis in guinea-pig isolated lungs perfused via the trachea. European Journal of Pharmacology 130, 249–55.CrossRefGoogle ScholarPubMed
Farrar, W. L. & Humes, J. L. (1985). The role of arachidonic acid metabolism in the activities of interleukin 1 and 2. Journal of Immunology 135, 1153–9.CrossRefGoogle ScholarPubMed
Parrel, J. P. & Kirkpatrick, C. E. (1987). Experimental cutaneous leishmaniasis. II. A possible role for prostaglandins in exacerbation of disease in Leishmania major-infected BALB/c mice. Journal of Immunology 138, 902–7.Google Scholar
Gillis, S., Perm, M. M., Ou, W. & Smith, K. A. (1978). The cell growth factor in parameters of production and quantitative microassay for activity. Journal of Immunology 120, 2027–32.CrossRefGoogle ScholarPubMed
Green, S. J., Meltzer, M. S., Hibbs, J. B. & Nacy, C. A. (1990). Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. Journal of Immunology 144, 278–83.CrossRefGoogle ScholarPubMed
Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L. & Locksley, R. M. (1989). Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Journal of Experimental Medicine 169, 59–72.CrossRefGoogle ScholarPubMed
Heinzel, F. P., Sadick, M. D., Mutha, S. S. & Locksley, R. M. (1991). Production of interferon γ, interleukin 2, interleukin 4, and interleukin 10 by CD44+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proceedings of the National Academy of Sciences, USA 88, 7011–15.CrossRefGoogle Scholar
Higgs, G. A., Flower, R. J. & Vane, J. R. (1979). A new approach to anti-inflammatory drugs. Biochemical Pharmacology 28, 1959–61.CrossRefGoogle ScholarPubMed
Higgs, G. A., Henderson, B., Moncada, S. & Salmon, J. A. (1985). The synthesis and inhibition of eicosanoids in inflammation. In Inflammatory Mediators (ed. Higgs, G. A. & Williams, T. J.), pp. 19–35. London: Macmillan.CrossRefGoogle Scholar
Howard, J. G., Hale, C. & Liew, F. Y. (1980). Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica. Journal of Experimental Medicine 152, 594–607.CrossRefGoogle ScholarPubMed
Howard, J. G., Hale, C. & Liew, F. Y. (1981). Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to Leishmania tropica. Journal of Experimental Medicine 153, 557–68.CrossRefGoogle ScholarPubMed
Kunkel, S. L., Spengler, M., May, M. A., Spengler, R., Larrick, j. & Remick, D. (1988). Prostaglandin E2regulates macrophage-derived tumor necrosis factor gene expression. Journal of Biological Chemistry 263, 5380–4.CrossRefGoogle ScholarPubMed
Liew, F. Y., Millott, S., Li, Y., Lelchuk, R., Chan, W. L. & Ziltener, H. (1989). Macrophage activation by interferon-gamma from host protective T-cell inhibited by interleukin (IL)-3 and IL-4 produced by disease-promoting T cells in leishmaniasis. European Journal of Immunology 19, 1227–32.CrossRefGoogle ScholarPubMed
Liew, F. Y., Millott, S., Parkinson, C., Palmer, R. M. J. & Moncada, s. (1990 a). Macrophage killing of leishmania parasite in vivo is mediated by nitric oxide from L-arginine. Journal of Immunology 144, 4794–7.CrossRefGoogle ScholarPubMed
Liew, F. Y., Li, Y. & Millott, s. (1990 b). Tumour necrosis factor (TNF) in leishmaniasis. II. TNF-induced macrophage leishmanicidal activity is mediated by nitric oxide from L-arginine. Immunology 71, 556–9.Google Scholar
McDonald, p. p., McColl, s. R., Naccache, p. H. & Borgeat, p. (1992). Activation of the human neutrophil 5-lipoxygenase by leucotriene B4. British Journal of Pharmacology 107, 226–30.CrossRefGoogle Scholar
Milano, S., Arcoleo, F., Dieli, M., D'agostino, R., D'agostino, P., De Nucci, G. & Cillari, E. (1995). Prostaglandin E2 regulates inducible nitric oxide synthase in the murine macrophage cell line J774. Prostaglandins. 49, 105–15.CrossRefGoogle ScholarPubMed
Mosmann, T. R. & Coffman, R. L. (1989). Th1 and Th2cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7, 145–73.CrossRefGoogle Scholar
Nickoloff, B. J. (1988). Role of interferon-γ in cutaneous trafficking of lymphocytes with emphasis on molecular and cellular adhesion events. Archives of Dermatology 124, 1835–43.CrossRefGoogle ScholarPubMed
Phipps, R. P., Stein, S. H. & Roper, R. L. (1991). A new view of prostaglandin E regulation of the immune response. Immunology Today 12, 349–52.CrossRefGoogle ScholarPubMed
Reiner, N. E. & Malemud, C. J. (1985). Arachidonic acid metabolism by murine peritoneal macrophages infected with Leishmania donovani: in vitro evidence for parasite-induced alterations in cyclooxygenase and lipoxygenase pathways. Journal of Immunology 134, 556–63.CrossRefGoogle ScholarPubMed
Renz, H., Gong, J. H., Schmidt, A., Nain, M. & Gemsa, D. (1988). Release of tumor necrosis factor from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. Journal of Immunology 141, 2388–93.CrossRefGoogle ScholarPubMed
Salmon, J. A. (1978). A radioimmunoassay for 6-keto-prostaglandin F1. Prostaglandins 15, 383–97.Google Scholar
Scott, P. (1991). IFN-γ modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. Journal of Immunology 147, 3149–55.CrossRefGoogle Scholar
Takii, T., Akahoshi, T., Kato, K., Hayashi, H., Marunouchi, T. & Onozaki, K. (1992). Interleukin-1 up-regulates transcription of its own receptor in a human fibroblast cell line TIG-1: role of endogenous PGE2 and cAMP. European Journal of Immunology 22, 1221–7.CrossRefGoogle Scholar
Yamaoka, K. A. & Kolb, J. P. (1993). Leukotriene B4induces interleukin 5 generation from human T lymphocytes. European Journal of Immunology 23, 2392–8.CrossRefGoogle ScholarPubMed
Zubiaga, A. M., Muñoz, E. & Huber, B. T. (1991). Production of IL-lα by activated Th type 2 cells. Its role as an autocrine growth factor. Journal of Immunology 146, 3849–56.CrossRefGoogle Scholar