Involvement of mitogen-activated protein kinases and nuclear factor-kappa B activation in nitric oxide-induced interleukin-8 expression in human pulp cells

Objective: This study examined the effect of nitric oxide (NO) on interleukin-8 (IL-8) production and the involvement of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in primary cultured human pulp cells. Study design: IL-8 production was measured using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. MAPK activation and IκB degradation and phosphorylation were determined by western blotting. Results: Sodium nitroprusside (SNP), an NO donor, has increased IL-8 secretion and mRNA expression in a dose- and time-dependent manner. SNP induced the phosphorylation of p38 MAPK and extracellular-regulated kinase (ERK), degradation and phosphorylation of IκB, and activation of NF-κB. Furthermore, inhibition of the ERK, p38, and NF-κB pathways blocked SNP-induced IL-8 secretion. Conclusion: Human pulp cells showed NO-induced IL-8 expression via the MAPK and NF-κB pathways, which may play an important role in the inflammatory responses of pulp and periapical lesions.