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

• Published in: Biological & pharmaceutical bulletin 2002, Vol.25(9), pp.1165-1168
• Main Authors: Kwon, Okyun, Lee, Eunkyung, Moon, Tae Chul, Jung, Hyejin, Lin, Chang Xiu, Nam, Kyung-Soo, Baek, Suck Hwan, Min, Hae-Ki, Chang, Hyeun Wook
• Format: Article
• Language: English
• Subjects: Air; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; cyclooxgenase-2 (COX-2); Cyclooxygenase 2; Cytokines - biosynthesis; Cytokines - genetics; Environmental pollutants toxicology; human leukemia mast cell; Humans; Inflammation - enzymology; Inflammation - metabolism; inflammatory cytokine; Isoenzymes - biosynthesis; Isoenzymes - genetics; Mast Cells - drug effects; Mast Cells - enzymology; Mast Cells - metabolism; Medical sciences; Membrane Proteins; NF-kappa B - metabolism; NF-kappa B - physiology; nuclear factor (NF)κB; polychlorinated biphenyl (PCB); Polychlorinated Biphenyls - chemistry; Polychlorinated Biphenyls - pharmacology; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; pyrrolidine dithiocarbamate (PDTC); RNA, Messenger - biosynthesis; Toxicology; Various organic compounds
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.25.1165

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 factor (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 2 h. 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.