Fig. 4. Involvement of p38MAPK and CREB in TGFβ1-induced expression of APRIL. (A) TGF-β1 induces APRIL mRNA expression via p38MAPK. P388D1 cells were pre-treated with 5 μM PD98059 (an ERK inhibitor), 10 μM SP600125 (a JNK inhibitor), 10 μM SB431542 (an inhibitor of ALK4, 5, and 7), or 10 μM SB203580 (a p38 MAPK inhibitor) for 1 h, and then stimulated with TGF-β1 (1 ng/ml) for 9 h. (B, C-1) Cells were transfected with 1 μg of the expression vectors for CREB or DN-CREB prior to treatment with TGF-β1 (1 ng/ml) for 9 h. Cells were pre-incubated with 5 μM SB203580 for 1 h. Levels of APRIL transcripts and APRIL protein were measured by RT-PCR (A, B) and Western blot (C-1), respectively. Fold increase values represent relative expression of APRIL normalized to expression of β-actin. (C-2) Western blot was performed to detect the expression of transfected CREB under the same conditions as in (B) and (C-1).