Details

Autor(en) / Beteiligte

• Faure, E
• Equils, O
• Sieling, P A
• Thomas, L
• Zhang, F X
• Kirschning, C J
• Polentarutti, N
• Muzio, M
• Arditi, M

Titel

Bacterial Lipopolysaccharide Activates NF- Kappa B through Toll-like Receptor 4 (TLR-4) in Cultured Human Dermal Endothelial Cells. Differential Expression of TLR-4 and TLR-2 in Endothelial Cells

Ist Teil von

• The Journal of biological chemistry, 2000-04, Vol.275 (15), p.11058-11063

Erscheinungsjahr

2000

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• A missense mutation in the cytoplasmic domain of the Toll-like receptor-4 (TLR-4) has been identified as the defect responsible for lipopolysaccharide (LPS) hyporesponsiveness in C3H/HeJ mice. TLR-4 and TLR-2 have recently been implicated in LPS signaling in studies where these receptors were overexpressed in LPS non- responsive 293 human embryonic kidney cells. However, the signaling role of TLR-4 or TLR-2 in human cells with natural LPS response remains largely undefined. Here we show that human dermal microvessel endothelial cells (HMEC) and human umbilical vein endothelial cells express predominantly TLR-4 but very weak TLR-2 and respond vigorously to LPS but not to Mycobacterium tuberculosis 19-kDa lipoprotein. Transient transfection of non-signaling mutant forms of TLR-4 and anti- TLR-4 monoclonal antibody inhibited LPS-induced NF- Kappa B activation in HMEC, while a monoclonal antibody against TLR-2 was ineffective. In contrast to LPS responsiveness, the ability of HMEC to respond to 19- kDa lipoprotein correlated with the expression of TLR-2. Transfection of TLR-2 into HMEC conferred responsiveness to 19-kDa lipoprotein. These data indicate that TLR-4 is the LPS signaling receptor in HMEC and that human endothelial cells (EC) express predominantly TLR-4 and weak TLR-2, which may explain why they do not respond to 19-kDa lipoprotein. The differential expression of TLRs on human EC may have important implications in the participation of vascular EC in innate immune defense mechanisms against various infectious pathogens, which may use different TLRs to signal.