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-kappa B activation.
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-1beta (IL-1beta), IL-6 and tumor necrosis factor (TNF)-alpha in the human leukemic mast cell line were investigated. TNF-alpha and IL-1beta 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)-kappaB pathway inhibitor, pyrrolidine dithiocarbamate, suppressed COX-2, TNF-alpha and IL-1beta induction and reduced the IL-6 mRNA levels induced by PCB. The NF-kappaB activity was determined by electrophoretic mobility shift analysis (EMSA) using an oligonucleotide containing a consensus NF-kappaB binding sequence. Stimulating the cells with PCB activated NF-kappaB. However, pre-treating them with a NF-kappaB pathway inhibitor, pyrrolidine dithiocarbamate, suppressed PCB-induced NF-kappaB activation. This suggests that PCB induces cycloxoygenase-2 and pro-inflammatory cytokine expression, and that this induction occurs through NF-kappaB.
Kwon
Okyun
O
College of Pharmacy, Yeungnam University, Gyongsan, Korea.
Lee
Eunkyung
E
Moon
Tae Chul
TC
Jung
Hyejin
H
Lin
Chang Xiu
CX
Nam
Kyung-Soo
KS
Baek
Suck Hwan
SH
Min
Hae-Ki
HK
Chang
Hyeun Wook
HW
D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008565:Membrane Proteins; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011078:Polychlorinated Biphenyls; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C014024:2,4,5,2',4',5'-hexachlorobiphenyl