Structure-dependent suppression of LPS-induced inflammation by C-DIMs
Primary murine mixed glial cultures were treated with saline or 1 μg/ml LPS and 1 or 10 μM doses of one of 14 C-DIM analogs. Structural differences displayed as R-Group, and significant suppression of NOS2 and IL-1β mRNA levels from LPS control are indicated. Data are expressed as mean ± S.D.; mRNA fold induction over LPS (β-actin internal control).
| C-DIM | R-Group | NOS2 mRNA (Fold-Induction) | IL-1β mRNA (Fold-Induction) | ||
|---|---|---|---|---|---|
| Saline 1.0 ± 0.2 | LPS 240.5 ± 24.4a | Saline 1.0 ± 0.2 | LPS 175.7 ± 16.5a | ||
| LPS + | LPS + | ||||
| C-DIM (1 μM) | C-DIM (10 μM) | C-DIM (1 μM) | C-DIM (10 μM) | ||
| 1 | -CF3 | 160.6 ± 13.1 | 50.8 ± 8.7b | 167.6 ± 18.2a | 34.1 ± 3.1b |
| 2 | -Br | 175.5 ± 34.9 | 73.1 ± 23.1 | 129.4 ± 43.0 | 40.6 ± 3.7b |
| 3 | -F | 133.8 ± 8.6 | 3.3 ± 1.5b | 156.7 ± 10.6a | 7.1 ± 1.8b |
| 4 | -tert-Butyl | 107.8 ± 20.5 | 84.8 ± 8.0 | 125.3 ± 8.0 | 93.9 ± 10.2 |
| 5 | -OCH3 | 141.4 ± 24.0 | 14.7 ± 4.7b | 142.6 ± 6.1a | 15.4 ± 2.3b |
| 6 | -N(CH3)2 | 224.2 ± 68.0a | 99.5 ± 21.7 | 164.9 ± 30.0a | 65.1 ± 9.1 |
| 7 | -H | 184.9 ± 36.1a | 12.4 ± 4.4b | 142.9 ± 44.5a | 12.6 ± 2.3b |
| 8 | -OH | 189.3 ± 61.8a | 0.7 ± 0.4b | 136.2 ± 48.3a | 9.3 ± 1.4b |
| 9 | -Phenyl | 136.2 ± 47.7 | 180.9 ± 34.5a | 137.4 ± 47.4a | 127.2 ± 5.8 |
| 10 | -CN | 96.0 ± 21.6 | 34.5 ± 5.8b | 140.1 ± 7.5a | 23.8 ± 1.8b |
| 11 | -CH3 | 140.0 ± 5.5 | 32.0 ± 6.8b | 152.2 ± 15.7a | 36.4 ± 3.5b |
| 12 | -Cl | 180.4 ± 26.2 | 60.6 ± 17.5b | 186.9 ± 27.6a | 45.9 ± 8.9b |
| 13 | -COOCH3 | 255.5 ± 78.8a | 90.9 ± 7.8b | 185.2 ± 11.5a | 44.0 ± 15.2b |
| 14 | -I | 242.9 ± 83.9a | 122.7 ± 33.5b | 161.4 ± 43.6a | 72.4 ± 15.0 |