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Titolo:
Noncleavable transmembrane mouse tumor necrosis factor-alpha (TNF alpha) mediates effects distinct from those of wild-type TNF alpha in vitro and in vivo
Autore:
Mueller, C; Corazza, N; Trachsel-Loseth, S; Eugster, HP; Buhler-Jungo, M; Brunner, T; Imboden, MA;
Indirizzi:
Univ Bern, Dept Pathol, Div Immunopathol, CH-3010 Bern, Switzerland Univ Bern Bern Switzerland CH-3010 munopathol, CH-3010 Bern, Switzerland Univ Zurich, Dept Clin Immunol, CH-8044 Zurich, Switzerland Univ Zurich Zurich Switzerland CH-8044 unol, CH-8044 Zurich, Switzerland ZLB Cent Lab, CH-3000 Bern, Switzerland ZLB Cent Lab Bern Switzerland CH-3000 ent Lab, CH-3000 Bern, Switzerland
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 53, volume: 274, anno: 1999,
pagine: 38112 - 38118
SICI:
0021-9258(199912)274:53<38112:NTMTNF>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEFICIENT MICE; METALLOPROTEINASE INHIBITOR; INTERLEUKIN-12 PRODUCTION; EXPERIMENTAL HEPATITIS; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; RECEPTOR; EXPRESSION; CELLS; RESPONSES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Mueller, C Univ Bern, Dept Pathol, Div Immunopathol, Murtenstr 31, CH-3010Bern, Switzerland Univ Bern Murtenstr 31 Bern Switzerland CH-3010 n, Switzerland
Citazione:
C. Mueller et al., "Noncleavable transmembrane mouse tumor necrosis factor-alpha (TNF alpha) mediates effects distinct from those of wild-type TNF alpha in vitro and in vivo", J BIOL CHEM, 274(53), 1999, pp. 38112-38118

Abstract

Tumor necrosis factor-alpha (TNF alpha) exists in two biologically active forms, a 26-kDa transmembrane form and a proteolytically cleaved and secreted form. We sequentially inactivated all three known cleavage sites of mouse TNF alpha by mutating the corresponding DNA sequences. A murine T cell hybridoma transfected with the nonsecretable mutant TNF alpha efficiently lysed L929 target cells in a cell contact-dependent manner and induced expression of vascular cell adhesion molecule-1 on mouse endothelioma cells. A genomic mouse TNF alpha clone encoding this mutant was subsequently introducedas a transgene into TNF alpha(-/-) lymphotoxin-alpha(-/-) mice. The 3' AU-rich regulatory elements of the TNF locus were maintained in the transgene to assure adequate gene regulation. Transmembrane TNF alpha transgenic micewere fully protected from endotoxic shock, and no TNF alpha bioactivity was detectable in the serum after stimulation with lipopolysaccharide. Activated CD4 T cells from these animals, however, lysed L929 cells in a cell contact-dependent way. After administration of Lipopolysaccharide, transmembrane TNF alpha transgenic mice produced significantly higher levels of interleukin-12 than wild-type mice or TNF-deficient mice. This indicates that transmembrane TNF alpha may greatly affect the course of a cellular immune responses in vivo and exerts quantitatively and qualitatively distinct functions from secreted TNF alpha in vitro and in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/21 alle ore 01:48:42