MD-2 Determinants of Nickel and Cobalt-Mediated Activation of Human TLR4
Fig 1
Nickel and cobalt trigger NF-κB activation, which is not inhibited by lipid IVa.
(A, B) Dose-dependent activation of human TLR4/MD-2 by nickel and cobalt. HEK293/hTLR4 cells were transfected with plasmid encoding hMD-2 and luciferase reporter plasmids. Cells were stimulated with LPS (0, 1, 5, 10, 100 ng/ml) and nickel (A) or cobalt (B) (0.10, 0.25, 0.50, 0.75, 1.0, 2.0, 4.0 mM) for 6 hours, lysed and tested for luciferase activity. (C) Copper and cadmium do not activate human TLR4/MD-2 receptor complex at low, non-toxic concentrations. (D) Tetraacylated lipid IVa (compound 406) does not inhibit human TLR4 activation by nickel or cobalt ions. #p≥0,01 (not significant); *p<0,01; ***p<0,0001 (t-test, compared to the unstimulated control unless indicated otherwise by brackets).