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Titolo:
The production of IFN-gamma by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4
Autore:
Schindler, H; Lutz, MB; Rollinghoff, M; Bogdan, C;
Indirizzi:
Univ Erlangen Nurnberg, Inst Klin Mikrobiol Immunol & Hyg, D-91054 Erlangen, Germany Univ Erlangen Nurnberg Erlangen Germany D-91054 -91054 Erlangen, Germany Univ Erlangen Nurnberg, Dept Dermatol, D-91054 Erlangen, Germany Univ Erlangen Nurnberg Erlangen Germany D-91054 -91054 Erlangen, Germany
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 5, volume: 166, anno: 2001,
pagine: 3075 - 3082
SICI:
0022-1767(20010301)166:5<3075:TPOIBI>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; HELPER TYPE-1 CELLS; INTERFERON-GAMMA; DENDRITIC CELLS; T-CELLS; LEISHMANIA-MAJOR; NATURAL-KILLER; TRANSCRIPTION; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Bogdan, C Univ Erlangen Nurnberg, Inst Klin Mikrobiol Immunol & Hyg, Wasserturmstr 3, D-91054 Erlangen, Germany Univ Erlangen Nurnberg Wasserturmstr 3 Erlangen Germany D-91054
Citazione:
H. Schindler et al., "The production of IFN-gamma by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4", J IMMUNOL, 166(5), 2001, pp. 3075-3082

Abstract

Macrophages release IFN-gamma on combined stimulation with IL-12 and IL-18, but the signaling requirements of this process and its regulation by other cytokines are unknown. Here, we demonstrate that STAT4 is indispensable for IL-12/LL-18-induced producHon of IFN-gamma by mouse peritoneal macrophages. Type 2 NO synthase (NOS2), which we previously found to be a prerequisite for IL-12-induced IFN- gamma production in NK cells, was not required for IFN-gamma production by these macrophages, IL-12 alone already induced the expression of IFN-gamma mRNA, but nuclear translocation of STAT4, the release of IFN-gamma protein, and the subsequent production of NO was strictlydependent on the simultaneous presence of IL-18, NF-kappaB, which mediatesIL-18 effects in T cells, was only weakly activated by IL-12 and/or IL-18 in macrophages. Known inhibitors of macrophage functions (e.g,, IL-4 and TGF-beta) also suppressed macrophage IFN-gamma production and the subsequent production of NOS2-derived NO. The inhibitory effect of IL-4 was paralleledby nuclear translocation of STAT6, which in EMSAs was able to bind to the same DNA oligonucleotide as STAT4, These results further define the production of IFN-gamma by macrophages and point to a diversity in the signals required for IFN-gamma production by various cell types.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 21:11:05