http://www.cnr.it/ontology/cnr/individuo/prodotto/ID12270
Cysteinyl Leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to STAT-1 mediated eosinophil adhesion. (Articolo in rivista)
- Type
- Label
- Cysteinyl Leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to STAT-1 mediated eosinophil adhesion. (Articolo in rivista) (literal)
- Anno
- 2008-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1124/jpet.107.131649 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Profita M; Sala A; Bonanno A; Siena L; Ferraro M; Di Giorgi R; Montalbano AM; Albano GD; Gagliardo R; Gjomarkaj M. (literal)
- Pagina inizio
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Istituto di Biomedicina e Immunologia Molecolare \"Alberto Monroy\" (literal)
- Titolo
- Cysteinyl Leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to STAT-1 mediated eosinophil adhesion. (literal)
- Abstract
- We studied the effect of leukotriene D4 (LTD4) on a human
bronchial epithelial cell line (16HBE) overexpressing the cysteinyl
leukotriene (CysLT) 1 receptor (HBECysLT1R), looking at
the associated signal transduction mechanisms as well as at
effects on inflammatory cell adhesion. The results obtained
showed that LTD4 increases the phosphorylation of extracellular
signal-regulated protein kinase (ERK) 1/2 and of the signal
transducer and activator of transcription 1 (STAT-1) in serine
727 (STAT-1Ser727), resulting in increased eosinophil adhesion
to HBECysLT1R, associated with enhanced surface expression
of intercellular adhesion molecule (ICAM) 1. Pretreatment with
a CysLT1R-selective antagonist or with a selective inhibitor
of protein kinase C (PKC) or with a selective inhibitor of the
mitogen-activated protein kinase kinase (MEK) successfully
suppressed both LTD4-induced STAT-1Ser727 phosphorylation
and the associated increase in eosinophil adhesion. The
use of the MEK inhibitor and of the selective CysLT1R antagonist
in electrophoretic mobility shift assay experiments showed
that LTD4 promotes the nuclear translocation of STAT-1
through the activation of ERK1/2 pathway. The key role of
STAT-1 in leukotriene D4 transduction signaling was confirmed
by RNA interference experiments, where silencing of STAT-1
expression abolished the effect of leukotriene D4 on eosinophil
adhesion. In conclusion, for the first time, we provide evidence
of the involvement of STAT-1 in the signal transduction mechanism
of the CysLT1 receptor; phosphorylation of STAT-1,
through PKC and ERK1/2 activation, causes enhanced ICAM-1
surface expression and eosinophil adhesion. Effective CysLT1R
antagonism may therefore contribute to the control of the
chronic inflammatory condition that characterizes human airways
in asthma. (literal)
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