Fig. 4

Possible involvements of PKC, ERK1/2, p38 MAPK, and NF-κB in CXCL8 production of acidic pH-stimulated ASMCs. ASMCs were pretreated with 10 μM bisindolylmaleimide I (BIM I), 10 μM U0126, 10 μM SB203580, 30 μM BAY11–7082, or control vehicle (0.1% DMSO) for 30 min. The cells were further incubated at the indicated pH with 10 μM BIM I, 10 μM U0126, 10 μM SB203580, 30 μM BAY11–7082, or control vehicle (0.1% DMSO) for an additional 24 h. CXCL8 secretion induced by extracellular acidification in ASMCs is significantly suppressed by U0126 and BIM I, but not SB203580. BAY11–7082 almost completely inhibits CXCL8 secretion in ASMCs. Data are expressed as percentages of CXCL8 values in the supernatants of pH 6.3-stimulated ASMCs without any inhibitors. The data are expressed as means ± SEM (n = 4, **, P < 0.01; *, P < 0.05; NS, not significant)