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Titolo:
Cell-mediated suppression of human interleukin-2 gene expression at splicing of mRNA
Autore:
Ketzinel, M; Kaempfer, R;
Indirizzi:
Hebrew,Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91010 Jerusalem Hebrew Univ Jerusalem Jerusalem Israel IL-91010 irol, IL-91010 Jerusalem
Titolo Testata:
IMMUNOLOGY LETTERS
fascicolo: 1, volume: 68, anno: 1999,
pagine: 161 - 166
SICI:
0165-2478(19990503)68:1<161:CSOHIG>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOCYTES-T; CYCLOPHOSPHAMIDE; SUBPOPULATIONS; DISTINCT;
Keywords:
human interleukin-2 gene regulation; immunosuppression; CD8 cells; mRNA splicing;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
13
Recensione:
Indirizzi per estratti:
Indirizzo: Kaempfer, R Hebrew,Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91010 Jerusalem Hebrew Univ Jerusalem Jerusalem Israel IL-91010 10 Jerusalem
Citazione:
M. Ketzinel e R. Kaempfer, "Cell-mediated suppression of human interleukin-2 gene expression at splicing of mRNA", IMMUNOL LET, 68(1), 1999, pp. 161-166

Abstract

Human IL-2 gene expression is regulated by cell-mediated suppression. Mitogenic stimulation of PBMC induces transient activation of CD8 cells that inhibit expression of this gene. Depletion of CD8 cells elicits marked superinduction of IL-2 mRNA; reintroduction of CD8 cells causes severe inhibition. Moreover, during IL-2 gene induction, splicing of IL-2 precursor transcripts becomes inhibited, resulting in a transient mRNA wave. This block in IL-2 mRNA splicing is relieved by the translation inhibitor, cycloheximide (CHX), which does not stimulate transcription [Gerez et al., J. Biol. Chem. 270, 15569 (1995)]. We show that suppression of IL-2 mRNA expression, whether by CD8 cells, soluble mediators derived from them, or IL-10, is relieved completely by CHX. Hence, suppression involves a CHX-sensitive step. Response to CHX, manifested in superinduction of IL-2 mRNA, is enhanced IO-fold during suppression. Suppression by CD8 cells or soluble mediators leads to rapid degradation of precursor transcripts while relief from suppression leads to a significant rise in precursor RNA. These changes precede effects atthe mRNA level. We conclude that suppression induces a block in mRNA splicing and degradation of blocked precursor transcripts. The near-complete absence of IL-2 mRNA superinduction by CHX in Jurkat Th cells, lacking cells with suppressive capacity, supports this interpretation. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 03:32:33