p38 MAP kinase and phospholipase A2 pathways are involved in ADAM-9–induced production of IL-6 by hOBs. hOBs were incubated in the presence or absence of inhibitors of p38 MAPK (SB-203580, 10 μM), MEK (PD-98059, 10 μM), cPLA2 (AACOCF3, 20 μM), cAMP (RP-cAMP, 10 μM), NF-κB (BAY 11-7082, 10 μM; and SN50, 10 μg/mL), or JAK2 (AG490 5 μM) for 30 minutes before addition of ADAM-9 (200 nM; A) or RPMI-8226 cells (5 × 105; B). The cells were incubated for a further 24 hours, and IL-6 concentrations were determined by ELISA. Data are the means of samples from a representative experiment (n = 4-8), and error bars are 95% CI. IL-6 production is shown as percentage of the mean + 95% CI of the maximum bar in the graph. A Mann-Whitney U test was used for the pair-wise comparisons. *P < .01 samples compared with respective untreated hOBs (□); †P < .01 samples compared with ADAM-9–treated hOBs (A) or hOBs cultured with RPMI-8226 cells (B).
