MD-2 Determinants of Nickel and Cobalt-Mediated Activation of Human TLR4
Fig 4
Activation of human TLR4 by metal ions requires different TLR4 and MD-2 residues than activation by endotoxin.
(A) hTLR4 amino acid residues that are essential for activation by LPS are not needed for activation by nickel or cobalt. HEK293 cells were transfected with luciferase reporter plasmids, plasmid encoding hMD-2 and plasmid encoding either wild type hTLR4 or the hTLR4 mutant hF440A. (B) hMD-2 amino acid residues that are essential for activation by LPS are not needed for activation by nickel or cobalt. HEK293/hTLR4 cells were transfected with luciferase reporter plasmids and with plasmid encoding either wild type or mutant hMD-2. #p≥0,01 (not significant); *p<0,01; **p<0,001; (t-test, compared to the unstimulated control (as indicated by brackets) or compared to the wt hTLR4 with the corresponding treatment).