P38 MAPK and NF-κB on IL-6 release in human gingival fibroblasts

The induction of interleukin-6 (IL-6) using a proinflammatory cytokine (IL-1 beta) was studied in human gingival fibroblasts (HGFs) in relation to p38 MAPK and NF-kappa B transcription factor. When added to HGFs, IL-1 beta had a stimulatory effect on the production of IL-6, and this effect was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release also was reduced by the addition of pyrrolidine dithiocarbamate or NF-kappa B SN50, which has been reported as potent NF-kappa B inhibitor. Both the NF-kappa B inhibitors in the presence of SB203580 had more inhibitory effect on IL-6 release. IL-1 beta stimulated NF-kappa B binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on the NF-kappa B activation, and both the NF-kappa B inhibitors failed to reduce the p38 MAPK activation in the IL-1 beta-stimulated HGFs. These results strongly suggest that both p38 MAPK and NF-kappa B are required in IL-1 beta-induced IL-6 synthesis and that these two IL-1 beta-activated pathways can be primarily dissociated.