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: 3.17). 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.

Download full-text

Full-text

Available from: Nataša Kopitar-Jerala, Nov 19, 2014
  • Source
    • "Cystatin A can also induce synthesis of tumor necrosis factor and interleukin 10, and stimulate nitric oxide production [41]. Therefore , Cystatin A may be able to change its expression level in certain pathologies and could play a diagnostic role. "
    [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.
    Full-text · Article · Feb 2015 · Journal of Pharmaceutical and Biomedical Analysis
  • Source
    • "Cystatins, a protein superfamily of reversible inhibitors of papainlike cysteine proteases, are found in plants, animals and microorganisms and which play essential roles in the physiology of all living organisms (Barrett, 1987; Turk et al., 2008). Functionally, Cystatins are involved in various physiological and cellular processes, including immune and inflammatory responses, protein homeostasis, pro-hormone processing, cellular matrix remodeling, and apoptosis (Synnes, 1998; Abrahamson et al., 2003; Kopitar-Jerala, 2006; Lefebvre et al., 2008; Shah and Bano, 2009; Premachandra et al., 2012). "
    [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.
    Full-text · Article · Nov 2014 · Journal of Asia-Pacific Entomology
  • Source
    • "The cystatins are endogenous, reversible and tight-binding inhibitors of the papain (C1) and legumain (C13) families of the cysteine proteases and have significant similarities in the amino acid sequence and in the protein structure [1] [2]. Stefin B (cystatin B) is an endogenous cysteine cathepsin inhibitor localized in the cytosol and nucleus, where it interacts with histones and cathepsin L [3]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Innate immune responses are tightly regulated to avoid excessive activation and subsequent inflammatory damage to the host, and interleukin-10 (IL-10) plays a crucial role in preventing inflammation. Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases. In stefin B-deficient bone marrow-derived macrophages (BMDMs), we detected an increase in the induction of the LPS-induced pro-inflammatory signal nitric oxide (NO) but decreased IL-10 expression. The phosphorylation of ERK and p38 MAP-kinases was significantly decreased in stefin B-deficient macrophages, as was STAT-3 phosphorylation. These findings show that stefin B influences the expression of anti-inflammatory IL-10 in response to the TLR4 agonist LPS.
    Full-text · Article · Jan 2014 · FEBS letters
Show more