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Titolo:
MOUSE INTERLEUKIN-12 (IL-12) P40 HOMODIMER - A POTENT IL-12 ANTAGONIST
Autore:
GILLESSEN S; CARVAJAL D; LING P; PODLASKI FJ; STREMLO DL; FAMILLETTI PC; GUBLER U; PRESKY DH; STERN AS; GATELY MK;
Indirizzi:
HOFFMANN LA ROCHE INC,DEPT INFLAMMAT AUTOIMMUNE DIS NUTLEY NJ 07110 HOFFMANN LA ROCHE INC,DEPT INFLAMMAT AUTOIMMUNE DIS NUTLEY NJ 07110 HOFFMANN LA ROCHE INC,DEPT BIOTECHNOL NUTLEY NJ 07110
Titolo Testata:
European Journal of Immunology
fascicolo: 1, volume: 25, anno: 1995,
pagine: 200 - 206
SICI:
0014-2980(1995)25:1<200:MI(PH->2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; ACTIVATED HUMAN LYMPHOBLASTS; RESPONSES; RECEPTOR; PROLIFERATION; INDUCTION; PROTEINS; BINDING; ALPHA;
Keywords:
INTERLEUKIN; INTERLEUKIN-12; INTERLEUKIN-12 P40 SUBUNIT; INTERLEUKIN-12 ANTAGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
S. Gillessen et al., "MOUSE INTERLEUKIN-12 (IL-12) P40 HOMODIMER - A POTENT IL-12 ANTAGONIST", European Journal of Immunology, 25(1), 1995, pp. 200-206

Abstract

Interleukin-12 (IL-12) is a cytokine that has regulatory effects on Tand natural killer (NK) cells and is composed of two disulfide-bondedsubunits, p40 and p35. It was recently reported that supernatants from cultures of mouse IL-12 (moIL-12) p40-transfected COS cells could inhibit IL-12-dependent responses in vitro (Mattner, F., et al., Eur. J. Immunol. 1993. 23: 2202). We have further characterized the nature ofthe inhibitory substance. Purified mouse p40 produced in a baculovirus expression system was found to consist of two species: the p40 monomer and a disulfide-linked p40 dimer [(p40)(2)]. The (p40)(2) was 25- to 50-fold more active than the p40 monomer in causing specific, dose-dependent inhibition of IL-12-induced mouse concanavalin A (Con A) blast proliferation and could also inhibit IL-12-induced interferon-gamma (IFN-gamma) secretion by mouse splenocytes and IL-12-dependent activation of mouse NK cells. Competitive binding studies on mouse Con A blasts showed that (p40)(2) was equally effective as moIL-12 in competing with I-125-labeled moIL-12 ([I-125]moIL-12) for binding to mouse Con Ablasts. However, in contrast to moIL-12, mouse (p40)(2) displayed little ability to compete with I-125-labeled human IL-12 (huIL-12) for binding to high-affinity IL-12 receptors (IL-12R) on human phytohemagglutinin (PI-IA) blasts and caused little or no inhibition of huIL-12-induced human PHA blast proliferation. Nonetheless, mouse (p40)(2) was equally effective as moIL-12 in competing with [I-125]huIL-12 for binding to COS cells transfected with the human IL-12R beta subunit and expressing low-affinity IL-12 binding sites. These results suggest that (i) the majority of the structural determinants required for binding of IL-12 to its receptor are contained within the p40 subunit, but p35 isrequired for signaling, (ii) the p40 subunit of 11,-12 interacts withthe beta subunit of IL-12R, and (iii) (p40)(2) may be a suitable IL-12 antagonist for studying the role of IL-12 in various immune responses in vice as well as in vitro. Further studies are required to determine whether or not (p40)(2) is produced by normal lymphoid cells and isa physiologic regulator of IL-12 activity.

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Documento generato il 29/09/20 alle ore 19:42:57