Expression of cyclooxygenase-2 and pro-inflammatory cytokines induced by 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) in human mast cells requires NF-κB activation

Abstract

Mast cells are critical for initiating innate immune and inflammatory responses by releasing a number of pro-inflammatory mediators. The potential immunomodulatory properties of hydrogenated aromatic hydrocarbons have been the subject of extensive investigation, as the immune system is a sensitive target for hydrogenated aromatic hydrocarbon toxicity. In this report, the effects of polychlorinated biphenyl (PCB) on the expression of cyclooxygenase-2 and pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis fac-tor (TNF)-α in the human leukemic mast cell line were investigated. TNF-α and IL-1β expressed their respective mRNA in the presence or absence of PCB, while cyclooxygenase-2 (COX-2) and IL-6 mRNA expression were highly induced by PCB after 2h. Moreover, pre-treatment with the nuclear factor (NF)-κB pathway inhibitor, pyrrolidine dithiocarbamate, suppressed COX-2, TNF-α and IL-1β induction and reduced the IL-6 mRNA levels induced by PCB. The NF-κB activity was determined by electrophoretic mobility shift analysis (EMSA) using an oligonucleotide containing a consensus NF-κB binding sequence. Stimulating the cells with PCB activated NF-κB. However, pre-treating them with a NF-κB pathway inhibitor, pyrrolidine dithiocarbamate, suppressed PCB-induced NF-κB activation. This suggests that PCB induces cycloxoygenase-2 and pro-inflammatory cytokine expression, and that this induction occurs through NF-κB.