Table 2.
Effects of roflumilast on TNFα, IL-13, TGFβ, CTGF, αI(I)collagen and endothelin-1 (ET-1) expression following bleomycin in mice
|
TNFα |
IL-13 |
TGFβ |
CTGF |
αI(I)collagen |
ET-1 |
|||
|---|---|---|---|---|---|---|---|---|
| mRNA (lung) | Protein (BALF) | Protein (BALF) | mRNA (lung) | Protein (BALF) | mRNA (lung) | mRNA (lung) | mRNA (lung) | |
| Control | 1.0 ± 0.2 | 25.7 ± 6.8 | 4.4 ± 0.9 | 1.1 ± 0.3 | 18.2 ± 10.9 | 1.1 ± 0.05 | 1.0 ± 0.2 | 1.0 ± 0.1 |
| BLM | 2.2 ± 0.2# | 76.8 ± 12.1# | 12.3 ± 1.4# | 6.2 ± 0.7# | 107.3 ± 18# | 4.6 ± 0.8# | 3.3 ± 0.7# | 4.1 ± 0.4# |
| BLM + ROF1 | 1.2 ± 0.2* | 45.4 ± 1.2* | 8.4 ± 1.0* | 3.8 ± 1* | 56 ± 16.5* | 2.3 ± 0.8* | 1.8 ± 0.4* | 2.2 ± 0.5* |
| BLM + ROF5 | 0.9 ± 0.4* | 40.9 ± 9* | 7.4 ± 1.3* | 2.7 ± 0.3* | 39 ± 10.1* | 1.5 ± 0.6* | 1.4 ± 0.2* | 2.0 ± 0.4* |
Roflumilast was administered at 1 or 5 mg·kg−1·d−1 (ROF1 or ROF5) p.o. from day 1 to 14 after intratracheal instillation of bleomycin (day 1, 3.75 U·kg−1) (preventive protocol). TNFα, IL-13 or TGFβ1 proteins were measured in BALF using ELISA. mRNA expression of TNFα, TGFβ1, CTGF, αI(I)collagen, ET-1 was measured in lung extracts by real-time quantitative PCR. Data shown are the means ± SEM of six (protein) or three to four (mRNA) animals. TNFα, IL-13 and TGFβ1 proteins are given in pg·mL−1, and mRNA as relative expression (i.e. x-fold change over control).
P < 0.05 from control;
P < 0.05 from bleomycin. Baseline expression remained unaffected by roflumilast (not shown).
CTGF, connective tissue growth factor; IL-13, interleukin-13; TGFβ, transforming growth factor-β; TNFα, tumour necrosis factor-α.