Publikationsdatum:
1999-05-13
Beschreibung:
Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diefenbach, A -- Schindler, H -- Rollinghoff, M -- Yokoyama, W M -- Bogdan, C -- New York, N.Y. -- Science. 1999 May 7;284(5416):951-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Klinische Mikrobiologie, Immunologie und Hygiene, Universitat Erlangen, Wasserturmstrasse 3, D-91054 Erlangen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320373" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
Cells, Cultured
;
Cyclic GMP/metabolism
;
Cytotoxicity, Immunologic
;
DNA-Binding Proteins/metabolism
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Immunity, Innate
;
Interferon-gamma/biosynthesis/genetics
;
Interferons/pharmacology
;
Interleukin-12/pharmacology/*physiology
;
Janus Kinase 2
;
Killer Cells, Natural/*immunology/metabolism
;
*Leishmania major
;
Leishmaniasis, Cutaneous/*immunology/metabolism
;
Lysine/analogs & derivatives/pharmacology
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Nitric Oxide/metabolism
;
Nitric Oxide Synthase/antagonists & inhibitors/*metabolism
;
Nitric Oxide Synthase Type II
;
Phosphorylation
;
Protein-Tyrosine Kinases/metabolism
;
Proteins/metabolism
;
*Proto-Oncogene Proteins
;
STAT4 Transcription Factor
;
*Signal Transduction
;
TYK2 Kinase
;
Trans-Activators/metabolism
;
Up-Regulation
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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