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Publication : Essential role of MD-2 in LPS responsiveness and TLR4 distribution.

First Author  Nagai Y Year  2002
Journal  Nat Immunol Volume  3
Issue  7 Pages  667-72
PubMed ID  12055629 Mgi Jnum  J:92494
Mgi Id  MGI:3053108 Doi  10.1038/ni809
Citation  Nagai Y, et al. (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat Immunol 3(7):667-72
abstractText  Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signaling in a variety of cell types. MD-2 is associated with the extracellular domain of TLR4 and augments TLR4-dependent LPS responses in vitro. We show here that MD-2(-/-) mice do not respond to LPS, do survive endotoxic shock but are susceptible to Salmonella typhimurium infection. We found that in MD-2(-/-) embryonic fibroblasts, TLR4 was not able to reach the plasma membrane and predominantly resided in the Golgi apparatus, whereas TLR4 was distributed at the leading edge surface of cells in wild-type embryonic fibroblasts. Thus, MD-2 is essential for correct intracellular distribution and LPS-recognition of TLR4.
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