Figure 1.
The overall structure of TNFR2-TNFα.
The model was homologically modeled with the templates 1tnr and 1a8m, the TNFβ-TNFR1 complex and a TNFα variant crystal structure. (A) The model structure of TNFR2-TNFα complex. TNFR2 are shown using purple and blue cartoons, while TNFα is in red. (B) The specific interactions of residue W89 (TRP) of TNFR2 with TNFα. (C) The specific interactions of residue E92 (Glu) of TNFR2 with TNFα.
Table 1.
The neutralizing activity of Etanercept and its variants on TNFα-induced cytotoxicity in mouse L929 cells.
Table 2.
The binding kinetics profiles of the Etanercept and W89Y/E92N to TNFα obtained by SPR.
Figure 2.
(A) Comparison of 1mg/kg Etanercept treated vs. the same dose of W89Y/E92N. (B) Comparison of 3mg/kg Etanercept treated vs. the same dose of W89Y/E92N. (C) Comparison of 9mg/kg Etanercept treated vs. the same dose of W89Y/E92N. Arrows indicate the time of treatment. *, **, a significant reduction of paw swelling of W89Y/E92N treatment compared to the groups given Etanercept (P<0.05; P<0.01 student t test). There were 10 rats per group. Black triangle, untreated group; Black diamond, 1mg/kg Etanercept treated group; White diamond, 1mg/kg W89Y/E92N treated group; Black square, 3 mg/kg Etanercept treated group; White square, 3mg/kg W89Y/E92N treated group; Black circle, 9 mg/kg Etanercept treated group; White circle, 9mg/kg W89Y/E92N treated group.
Table 3.
The alleviation effect of W89Y/E92N and Etanercept treatment on paw swelling in the rat model of CIA.
Figure 3.
Representative joint histopathology of the groups with CIA administered with W89Y/E92N and Etanercept.
Tissue sections from each group were stained with hematoxylin and eosin (HE). (A) None-immune group. (B) Untreated group treated with normal saline. (C) W89Y/E92N 1mg/kg treated group. (D) Etanercept 1mg/kg treated group. (E) W89Y/E92N 3mg/kg treated group. (F) Etanercept 3mg/kg treated group. (G) W89Y/E92N 9mg/kg treated group. (H) Etanercept 9mg/kg treated group. Scale shown on the right-hand side of (H) is equivalent to 0.1 mm.