Lipopolysaccharide enhances transforming growth factor ß1-induced platelet-derived growth factor-B expression in bile duct epithelial cells.
J Gastroenterol Hepatol
; 27(4): 714-21, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-22004089
ABSTRACT
BACKGROUND AND AIM:
Platelet-derived growth factor (PDGF)-B is a potent profibrogenic mediator expressed by bile duct epithelial cells (BDECs) that contributes to liver fibrosis after bile duct ligation. However, the mechanism of PDGF-B induction in BDECs during cholestasis is not known. Transforming growth factor ß (TGFß) and lipopolysaccharide (LPS) also contribute to the profibrogenic response after bile duct ligation. We tested the hypothesis that LPS and TGFß1 synergistically induce PDGF-B expression in BDECs.METHODS:
Transformed human BDECs (MMNK-1 cells) and primary rat BDECs were stimulated with LPS and/or TGFß1, and signaling pathways through which LPS potentiates TGFß1-induced PDGF-B mRNA expression were investigated.RESULTS:
Stimulation of MMNK-1 cells with LPS alone did not significantly induce PDGF-B mRNA expression. However, LPS co-treatment enhanced TGFß1 induction of PDGF-B mRNA in MMNK-1 cells and also in primary rat BDECs. Importantly, co-treatment of MMNK-1 cells with LPS and TGFß1 also significantly increased PDGF-BB protein expression. Interestingly, LPS did not affect TGFß1 activation of a SMAD-dependent reporter construct. Rather, stimulation of MMNK-1 cells with LPS, but not TGFß1, increased JNK1/2 phosphorylation. Expression of dominant negative JNK2, but not dominant negative JNK1, inhibited the LPS potentiation of TGFß1-induced PDGF-B mRNA expression in MMNK-1 cells. In addition, LPS treatment caused IκBα degradation and activation of a nuclear factor κB (NFκB)-dependent reporter construct. Expression of an IκBα super repressor inhibited activation of NFκB and attenuated LPS potentiation of TGFß1-induced PDGF-B mRNA.CONCLUSIONS:
The results indicate that LPS activation of NFκB and JNK2 enhances TGFß1-induced PDGF-B expression in BDECs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ductos Biliares
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Transdução de Sinais
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Lipopolissacarídeos
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Proteínas Proto-Oncogênicas c-sis
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Células Epiteliais
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Fator de Crescimento Transformador beta1
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article