Figure 4. Involvement of MAPK, NF-B, and PLC on the synergistic effects. (A,B) Gingival fibroblasts were pre-treated with or without PD98059, SP600125, SB203580, and/or PDTC at the dose indicated for 1 hr. The cells were then incubated with or without histamine (100 µmol/L) alone (A) or in the presence or absence of histamine (100 µmol/L) and TNF- (1 ng/mL) (B) for 8 hrs. (C) Gingival fibroblasts were pre-treated with or without U73122 or U73343 at the dose indicated for 30 min. The cells were then incubated in the presence or absence of histamine (100 µmol/L) and TNF- (10 ng/mL) for 8 hrs. After incubation, the supernatants were collected, and the concentrations of IL-8 in the supernatants were determined by ELISA. The results are expressed as the mean ± SD for triplicate cultures. *p < 0.05, and **p < 0.01 compared with no inhibitor.