Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Lipopolysaccharide-induced Notch signaling activation through JNK-dependent pathway regulates inflammatory response. | Tsao et al. Journal of Biomedical Science 2011 18 56 http content 18 1 56 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Lipopolysaccharide-induced Notch signaling activation through JNK-dependent pathway regulates inflammatory response 1 2 3 2 1 1 Po-Nien Tsao Shu-Chen Wei Miao-Tzu Huang Ming-Cheng Lee Hung-Chieh Chou Chien-Yi Chen and Wu-Shiun Hsieh1 Abstract Background Notch and TLR pathways were found to act cooperatively to activate Notch target genes and to increase the production of TLR-induced cytokines in macrophages. However the mechanism of LPS-induced Notch activation and its role in sepsis still remains unclear. Methods We analyzed the expression patterns of Notch components in a LPS-stimulated murine macrophage cell line using real-time PCR and western blotting. The role of DAPT a gamma-secretase inhibitor that is known to be a potent Notch inhibitor in LPS-induced cytokine release and experimental sepsis in mice was also explored. Student s t-test was used to analyze the difference between the two groups. Results We found that Notch signaling was activated after LPS stimulation. The expression of Jagged 1 a Notch ligand induced by LPS occurred in a JNK-dependent manner. In addition Notch target genes were upregulated by early Notch-independent activation followed by delayed Notch-dependent activation after LPS stimulation. Disruption of Notch signaling by DAPT attenuated the LPS-induced inflammatory responses including vascular endothelial growth factor VEGF and high-mobility group box chromosomal protein 1 HMGB1 both in vitro and in vivo and partially improved experimental sepsis survival. Conclusions These findings support the existence of a synergistic effect of Notch signaling and the LPS pathway both in vitro and in vivo. Therefore in the future Notch inhibitors may be utilized as adjunctive agents for the .
