Article

The role of cystatins in cells of the immune system

Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia.
FEBS Letters (Impact Factor: 3.34). 12/2006; 580(27):6295-301. DOI: 10.1016/j.febslet.2006.10.055
Source: PubMed

ABSTRACT The cystatins constitute a large group of evolutionary related proteins with diverse biological activities. Initially, they were characterized as inhibitors of lysosomal cysteine proteases - cathepsins. Cathepsins are involved in processing and presentation of antigens, as well as several pathological conditions such as inflammation and cancer. Recently, alternative functions of cystatins have been proposed: they also induce tumour necrosis factor and interleukin 10 synthesis and stimulate nitric oxide production. The aim of the present review was the analysis of data on cystatins from NCBI GEO database and the literature, and obtained in microarray and serial analysis of gene expression (SAGE) experiments. The expression of cystatins A, B, C, and F in macrophages, dendritic cells and natural killer cells of the immune system, during differentiation and activation is discussed.

0 Bookmarks
 · 
67 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Substance abuse is a risk factor for HIV infection and progression to AIDS. Recent evidence establishes that cocaine use promotes brain perivascular macrophage infiltration and microglia activation. The lysosomal protease cathepsin B is increased in monocytes from patients with HIV dementia and its secretion induces 10-15 % of neurotoxicity. Here we asked if cocaine potentiates cathepsin B secretion from HIV-infected monocyte-derived macrophages (MDM) and its effect in neuronal apoptosis. Samples of plasma, CSF, and post-mortem brain tissue from HIV positive patients that used cocaine were tested for cathepsin B and its inhibitors to determine the in vivo relevance of these findings. MDM were inoculated with HIV-1ADA, exposed to cocaine, and the levels of secreted and bioactive cathepsin B and its inhibitors were measured at different time-points. Cathepsin B expression (p < 0.001) and activity (p < 0.05) increased in supernatants from HIV-infected cocaine treated MDM compared with HIV-infected cocaine negative controls. Increased levels of cystatin B expression was also found in supernatants from HIV-cocaine treated MDM (p < 0.05). A significant increase in 30 % of apoptotic neurons was obtained that decreased to 5 % with the specific cathepsin B inhibitor (CA-074) or with cathepsin B antibody. Cathepsin B was significantly increased in the plasma and post-mortem brain tissue of HIV/cocaine users over non-drug users. Our results demonstrated that cocaine potentiates cathepsin B secretion in HIV-infected MDM and increase neuronal apoptosis. These findings provide new evidence that cocaine synergize with HIV-1 infection in increasing cathepsin B secretion and neurotoxicity.
    Journal of Neuroimmune Pharmacology 09/2014; 9(5). DOI:10.1007/s11481-014-9563-z · 3.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A method based on liquid chromatography/high resolution tandem mass spectrometry coupled with electrophoretic separation, for determination and relative quantification of the protein composition of exhaled breath condensate (EBC), was developed. Application of the procedure to a sample of EBC, pooled from nine healthy subjects, resulted in the identification of 167 unique gene products, 113 of which not previously reported in EBC samples. The abundance of the protein identified was estimated by means of the exponentially modified protein abundance index protocol (emPAI). Cytokeratins were by far the most abundant proteins in EBC samples. Many of the identified proteins were associated with multiple cellular location with cytoplasm constituting the largest group. Cytosol, nucleus, membrane, cytoskeleton and extracellular were other abundantly represented locations. No amylase was detected, suggesting the absence of saliva protein contamination. The profile obtained represents the most comprehensive protein characterization of EBC so far reported and demonstrates that this approach provides a powerful tool for investigating the protein profile of EBC samples. Compared with analogous investigations, this study also shows that the protein profile of EBC is strongly affected by the sampling method adopted.
    Journal of Pharmaceutical and Biomedical Analysis 02/2015; 105. DOI:10.1016/j.jpba.2014.11.050 · 2.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cystatins are involved in various physiological and cellular processes, including immune responses, protein homeostasis, signaling pathways, and apoptosis. Thus far, no Cystatins have been identified from spider venom. In this study, we report the cloning and characterization of a spider venom-derived Cystatin from Araneus ventricosus (AvCystatin). The AvCystatin gene contains an open reading frame of 405 bp encoding a predicted protein of 134-amino acids with a 16-amino acid signal peptide. Sequence alignment and structural modeling indicated that AvCystatin is closely related to family 2 Cystatins. Endogenous AvCystatin was present as an 18-kDa peptide in spider venom. Recombinant AvCystatin, expressed in baculovirus-infected insect cells, showed inhibitory activity against papain (Ki 86.73 nM), but not trypsin and chymotrypsin, defining a role for AvCystatin as a spider venom-derived cysteine protease inhibitor. Furthermore, recombinant AvCystatin exhibited stability against high temperatures and pH extremes, but had no effects on the growth of the entomopathogenic fungi Beauveria bassiana. These data demonstrate that AvCystatin is a novel member of the family 2 Cystatins and provide new insight for the future investigations of spider venom-derived Cystatins.
    Journal of Asia-Pacific Entomology 11/2014; 18(1). DOI:10.1016/j.aspen.2014.10.009 · 0.88 Impact Factor

Full-text (2 Sources)

Download
4 Downloads
Available from
Nov 19, 2014