system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Analysis of Variance, Animals, Bile Ducts, Cells, Cultured, Epithelial Cells, Humans, I-kappa B Proteins, Lipopolysaccharides, Mitogen-Activated Protein Kinase 9, NF-KappaB Inhibitor alpha, NF-kappa B, Phosphorylation, Proto-Oncogene Proteins c-sis, RNA, Messenger, Rats, Signal Transduction, Smad Proteins, Statistics, Nonparametric, Transforming Growth Factor beta1.
user
Does lipopolysaccharide enhance transforming growth factor β1-induced platelet-derived growth factor-B expression in bile duct epithelial cells? Context: 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 β (TGFβ) and lipopolysaccharide (LPS) also contribute to the profibrogenic response after bile duct ligation. We tested the hypothesis that LPS and TGFβ1 synergistically induce PDGF-B expression in BDECs. Transformed human BDECs (MMNK-1 cells) and primary rat BDECs were stimulated with LPS and/or TGFβ1, and signaling pathways through which LPS potentiates TGFβ1-induced PDGF-B mRNA expression were investigated. Stimulation of MMNK-1 cells with LPS alone did not significantly induce PDGF-B mRNA expression. However, LPS co-treatment enhanced TGFβ1 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 TGFβ1 also significantly increased PDGF-BB protein expression. Interestingly, LPS did not affect TGFβ1 activation of a SMAD-dependent reporter construct. Rather, stimulation of MMNK-1 cells with LPS, but not TGFβ1, increased JNK1/2 phosphorylation. Expression of dominant negative JNK2, but not dominant negative JNK1, inhibited the LPS potentiation of TGFβ1-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 TGFβ1-induced PDGF-B mRNA.
assistant
The results indicate that LPS activation of NFκB and JNK2 enhances TGFβ1-induced PDGF-B expression in BDECs. Final Decision: yes