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Titolo:
The selective proteasome inhibitors lactacystin and epoxomicin can be usedto either up- or down-regulate antigen presentation at nontoxic doses
Autore:
Schwarz, K; de Giuli, R; Schmidtke, G; Kostka, S; van den Broek, M; Kim, KP; Crews, CM; Kraft, R; Groettrup, M;
Indirizzi:
Kantonsspital, Res Dept, Lab Forsch Abt, CH-9007 St Gallen, Switzerland Kantonsspital St Gallen Switzerland CH-9007 -9007 St Gallen, Switzerland Max Delbruck Ctr Mol Med, Berlin, Germany Max Delbruck Ctr Mol Med Berlin Germany ck Ctr Mol Med, Berlin, Germany Univ Zurich Hosp, Inst Expt Immunol, Dept Pathol, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 ular & Dev Biol, New Haven, CT 06520 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 12, volume: 164, anno: 2000,
pagine: 6147 - 6157
SICI:
0022-1767(20000615)164:12<6147:TSPILA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CLASS-I MOLECULES; T-CELL EPITOPE; 20S PROTEASOME; ACTIVE-SITES; GENERATION; PROTEIN; PEPTIDES; DEGRADATION; PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Groettrup, M Kantonsspital, Res Dept, Lab Forsch Abt, Haus 09, CH-9007 St Gallen, Switzerland Kantonsspital Haus 09 St Gallen Switzerland CH-9007 tzerland
Citazione:
K. Schwarz et al., "The selective proteasome inhibitors lactacystin and epoxomicin can be usedto either up- or down-regulate antigen presentation at nontoxic doses", J IMMUNOL, 164(12), 2000, pp. 6147-6157

Abstract

The complete inhibition of proteasome activities interferes with the production of most MHC class I peptide ligands as well as with cellular proliferation and survival. In this study we have investigated how partial and selective inhibition of the chymotrypsin-like activity of the proteasome by theproteasome inhibitors lactacystin or epoxomicin would affect Ag presentation, At 0.5-1 mu M lactacystin, the presentation of the Lymphocytic choriomeningitis virus-derived epitopes NP118 and GP33 and the mouse CMV epitope pp89-168 were reduced and were further diminished in a dose-dependent manner with increasing concentrations. Presentation of the lymphocytic choriomeningitis virus-derived epitope GP276, in contrast, was markedly enhanced at low, but abrogated at higher, concentrations of either lactacystin or epoxomicin, The inhibitor-mediated effects were thus epitope specific and did not correlate with the degradation rates of the involved viral proteins. Although neither apoptosis induction nor interference with cellular proliferationwas observed at 0.5-1 mu M lactacystin in vivo, this concentration was sufficient to alter the fragmentation of polypeptides by the 20S proteasome invitro. Our results indicate that partial and selective inhibition of proteasome activity in vivo is a valid approach to modulate Ag presentation, with potential applications for the treatment of autoimmune diseases and the prevention of transplant rejection.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 09:52:43