Cellular and Molecular Life Sciences CMLS

, Volume 59, Issue 9, pp 1503-1512

First online:

Immunomodulatory properties of cystatins

  • B. VrayAffiliated withLaboratoire d'Immunologie Expérimentale (CP 615), Faculté de Médecine, Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels (Belgium), Fax +32 2 555 63 60, e-mail: bvray@ulb.ac.de
  • , S. HartmannAffiliated withChair of Molecular Parasitology, Humboldt-University, Berlin (Germany)
  • , J. HoebekeAffiliated withImmunologie et Chimie Thérapeutiques, UPR9021 du CNRS, Strasbourg (France)

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Abstract.

Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. Because these cysteine proteases exist in all living organisms and because they are involved in various biological and pathological processes, the control of these protease functions by cystatins is of cardinal importance. Cystatins are found in mammals but cystatin-like molecules are also present in mammals and parasites. In the immune system, cystatins modulate cathepsin activities and antigen presentation. They also induce tumor necrosis factor α and interleukin 10 synthesis, and they stimulate nitric oxide production by interferon γ-activated murine macrophages. In turn, nitric oxide has inhibitory activity on cysteine proteases, especially those from parasitic protozoa. Cystatins isolated from parasitic nematodes also have immunomodulatory activities that are distinguishable from those induced by lipopolysacharide-like molecules from endosymbiotic bacteria. On the whole, cystatins and cystatin-like molecules belong to a new category of immunomodulatory molecules. Doubtless increasing data will improve our knowledge of this property, leading to practical applications in immunotherapy.

Key words. Cystatins; cytokines; NO; antigen presentation; parasitic protozoa; nematodes.