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Publication : Inhibition of clathrin/dynamin-dependent internalization interferes with LPS-mediated TRAM-TRIF-dependent signaling pathway.

First Author  Wang Y Year  2012
Journal  Cell Immunol Volume  274
Issue  1-2 Pages  121-9
PubMed ID  22341560 Mgi Jnum  J:188180
Mgi Id  MGI:5439667 Doi  10.1016/j.cellimm.2011.12.007
Citation  Wang Y, et al. (2012) Inhibition of clathrin/dynamin-dependent internalization interferes with LPS-mediated TRAM-TRIF-dependent signaling pathway. Cell Immunol 274(1-2):121-9
abstractText  Recognition of lipopolysaccharide (LPS) by Toll-like receptor 4 (TLR4) activates two district proinflammatory signaling pathway and initiates LPS internalization. To investigate roles of LPS internalization, a traditionally regarded metabolic pathway for LPS, in regulation of these two pathways, three internalization inhibitors, monodansylcadaverine (MDC, a clathrin inhibitor), dynasore (DS, a dynamin inhibitor) and chloroquine (CQ, an endosome acidifying maturation inhibitor) were applied to induce internalization dysfunction in macrophages. Results showed MDC and DS affected LPS internalization but did not interfere with their colocalization. Additionally, they decreased cytokines and chemokines release and inhibited signaling molecules activation mediated by TRAM-TRIF-dependent pathway as determined by protein array. In contrast, CQ did not inhibit LPS internalization but affected the colocalization. It also suppressed macrophage activation mediated by both MyD88-dependent and TRAM-TRIF-dependent pathways. The above data indicated that LPS internalization was clathrin/dynamin dependent and it was essential for activation of TRAM-TRIF-dependent signaling pathway.
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