Disease relevance of Ctss

• These data identify selective inhibition of cysteine protease cathepsin S as a potential therapeutic strategy for autoimmune disease processes [1].
• These findings establish a pivotal role for Cat S in atherogenesis [2].
• Studies described here examine the functional significance of cathepsin S inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for Sjögren syndrome [1].
• Mice whose APC lack cathepsin S have reduced crosspriming to particulate and cell-associated antigens, as well as to influenza virus [3].
• Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis [4].

Psychiatry related information on Ctss

• Cathepsin S and TGF-beta1 were elevated more than 15-fold in mice and rats infected with two different CJD strains, but not in CJD-infected hamsters [5].

High impact information on Ctss

• These events reflect a developmental regulation of invariant (Ii) chain cleavage, most likely by the cysteine protease cathepsin S [6].
• Thus, the ratio of cystatin C to cathepsin S in developing DCs helps to determine the fate of newly synthesized MHC class II molecules [6].
• In immature DCs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the transport of class II-Ii chain complexes to lysosomes, while in mature DCs, elevated cathepsin S activity results in efficient delivery of class II alphabeta dimers to the plasma membrane [6].
• Cathepsin S overexpression in DCs decreased intracellular MHCII alphabeta dimer, Ii, and H2-DM levels, LPS-mediated surface expression of MHCII and suppressed CD4(+) T cell activation [7].
• IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells [7].

Biological context of Ctss

• Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo [8].
• PURPOSE: We recently used microarray and reverse transcriptase PCR (RT-PCR) analysis to show an upregulation of cathepsin S (CatS) and glutathione peroxidase 3 (GPX3) in the aging mouse RPE/choroid [9].
• Although cathepsin S-deficient mice have normal numbers of B and T cells and normal IgE responses, they show markedly impaired antibody class switching to IgG2a and IgG3 [10].
• The reversible downregulation of cathepsin S activity led to the transient accumulation of invariant chain-MHC class II complexes in MVBs [11].
• In contrast, phagosome biogenesis in bone marrow-derived dendritic cells (DCs) and macrophages preferentially involves endocytic compartments enriched in cathepsin S [12].

Anatomical context of Ctss

• Furthermore, we report that nonprofessional APC present a class II-bound endogenous peptide to naive CD4 T cells in vivo in a Cat S-dependent fashion [8].
• Unexpectedly, we found that murine Cat S plays a critical role in invariant chain degradation in intestinal epithelial cells [8].
• To examine this issue, we generated embryonic fibroblast lines that express CL, CS, or neither [13].
• The cysteine endoprotease cathepsin S mediates degradation of the MHC class II invariant chain Ii in human and mouse antigen-presenting cells [1].
• BACKGROUND: Cathepsin S is a member of the family of cysteine lysosomal proteases preferentially expressed in macrophages and microglia and is active after prolonged incubation in neutral pH [14].

Associations of Ctss with chemical compounds

• Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian elastases known [2].
• Cathepsins F or K partially degraded lipid-free apoA-I and reduced its ability to induce cholesterol efflux, whereas cathepsin S totally degraded apoA-I, leading to complete loss of apoA-I cholesterol acceptor function [15].
• Corpus luteum was the predominant location of cathepsin L. The distribution of cathepsin S resembled that of cathepsin L. The developing oocyte stained positive for all cathepsins [16].
• Epoxy succinate peptide derivatives, CLIK-066, 088, 112, 121, 148, 181, 185 and 187, are typical specific inhibitors for cathepsin L. Aldehyde derivatives CLIK-060 and CLIK-164 showed specific inhibition against cathepsin S and cathepsin K, respectively [17].
• It is shown that MGX (methylglyoxal), GO (glyoxal) and glycolaldehyde, but not hydroxyacetone and glucose, inhibit catB (cathepsin B), catL (cathepsin L) and catS (cathepsin S) activity in macrophage cell lysates, in a concentration-dependent manner [18].

Regulatory relationships of Ctss

• Cathepsin S regulates the expression of cathepsin L and the turnover of gamma-interferon-inducible lysosomal thiol reductase in B lymphocytes [19].
• Cathepsin S (CTSS) is a cysteine protease that is constitutively expressed in APCs and mediates processing of MHC class II-associated invariant chain [20].
• Overexpression of cystatin C suppressed IL-6-STAT3-mediated increase of cathepsin S activity and reduction of MHCII alphabeta dimer, Ii, and H2-DM levels in DCs [7].

Other interactions of Ctss

• Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice [2].
• Identification of the increased expression of monocyte chemoattractant protein-1, cathepsin S, UPIX-1, and other genes in dystrophin-deficient mouse muscles by suppression subtractive hybridization [21].
• One of them, cathepsin S, is present in the retinal pigment epithelium and affects the proteolytic processing by cathepsin D of diurnally shed photoreceptor outer segments [22].
• Hypothetically, it appears possible that retinal cystatin C, given its localization to the pigment epithelium and its ability to inhibit cathepsin S, could be involved in the regulation of photoreceptor degradation [22].
• To investigate the regulation of lysosomal enzymes during carcinogenesis, we measured cathepsins (Cats) D, B, and L in MCF-10F, which is a human breast epithelial cell line, and cells evolved after treatment with carcinogen and transfected with c-Ha-ras oncogene [23].

Analytical, diagnostic and therapeutic context of Ctss

• Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice [24].
• 1. Chromatin immunoprecipitation experiments show binding of PU.1 with the CTSS promoter in this same region [20].
• A 20-kilobase pair genomic clone of the human cathepsin S gene was isolated from a human fibroblast genomic library and used to map the human cathepsin S gene to chromosome 1q21 by fluorescence in situ hybridization [25].
• Results of Northern blotting using probes for human cathepsins B, L, and S are consistent with this hypothesis; only cathepsin S shows a restricted tissue distribution, with highest levels in spleen, heart, and lung [25].
• Quantitative real-time reverse transcription PCR and Western analyses confirmed the elevated levels of glial fibrillary acidic protein, complement component C1q, and cathepsin S, up-regulation of which has been associated with inflammatory responses in various neurodegenerative processes [26].

References