IL-12-dependent nuclear factor-kappaB activation leads to de novo synthesis and release of IL-8 and TNF-alpha in human neutrophils.
J Leukoc Biol
; 72(5): 995-1002, 2002 Nov.
Article
em En
| MEDLINE
| ID: mdl-12429722
ABSTRACT
The cytokine interleukin (IL)-12 plays a bridging role between innate and adaptive immunity. Here, we demonstrate that treatment of neutrophils with IL-12 leads to a transient increase in intracellular-free calcium [Ca(+)(+)](i) levels, which is necessary for the production of reactive oxygen metabolites (ROM). This production is associated with the activation and nuclear translocation of the transcription factor nuclear factor (NF)-kappaB and is inhibited in the presence of the intracellular calcium chelator 1,2-bis(O-amminophenoxy) ethane-N,N-N',N'-tetraacetic acid-acetoxymethyl ester and the ROM production inhibitor diphenyl iodonium. We show that IL-12 causes a significant increase in total mRNA levels, which appear dependent on the generated ROM. In addition IL-12 induces the de novo synthesis and production of IL-8 and tumor necrosis factor alpha (TNF-alpha) in a calcium- and ROM-dependent manner. Our data demonstrate a direct role for IL-12 in the activation of human neutrophils and suggest a ROM-dependent interplay between IL-12-induced [Ca(+)(+)](i) transient and the release of IL-8 and TNF-alpha through NF-kappaB activation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-8
/
NF-kappa B
/
Fator de Necrose Tumoral alfa
/
Interleucina-12
/
Neutrófilos
Limite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Arábia Saudita