In vivo effects of STA-5326 in inflammatory bowel disease animal model. (A) Photomicrographs of representative H&E-stained colons in CD4+ CD45RBhigh T-cell–transferred SCID mice, acquired by Eclipse E800 microscope (Nikon, Tokyo, Japan). (Ai) vehicle control. (Aii) Mouse treated with STA-5326 at 10 mg/kg given orally. (Aiii) Normal control without cell transfer. The original magnification is equivalent to ×40 (4×/0.13 NA objective, 10× eyepiece) in all 3 photographs, this showing the greater colon size in the vehicle control colon relative to the STA-5326–treated colon and the control group without T-cell transfer. (B) Higher magnification (original, ×200; 20×/0.50 NA objective, 10× eyepiece) photomicrographs. (Bi) Vehicle control. (Bii) STA-5326. (Biii) Normal control. (C) Histologic scoring of the distal colon sections. The extent of colonic inflammation was graded on a scale of 0 to 3 in each of 4 criteria: crypt elongation, cell infiltration, depletion of goblet cells, and the number of crypt abscesses. Results shown are mean ± SEM histology scores for each group. The severity of STA-5326–treated mice was significantly reduced compared with the level of vehicle group (*P < .05). (D) Percentage of colon weight relative to body weight in CD4+ CD45RBhigh T-cell transfer SCID mice and normal control mice without cell transfer. Each dot represents an individual mouse, and the bar drawn in each group represents the mean value. **P < .01 compared with the level of the vehicle group. (E) IFN-γ produced from LPMCs after stimulation by anti-CD3/anti-CD28 antibodies. LP lymphocytes were isolated from freshly obtained colonic specimens, and stimulated with immobilized anti-CD3ϵ antibody and soluble anti-CD28 antibody. Culture supernatants were assayed for IFN-γ production. Each dot represents an individual mouse, and the bar drawn in each group represents mean value. *P < .05 compared with the level of the vehicle group.
