Aryl hydrocarbon receptor-dependent inhibition of AP-1 activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in activated B cells.
B cells have been identified as sensitive cellular targets responsible for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated suppression of humoral immunity. In previous studies, TCDD was shown to produce a significant inhibition of IgM secretion and mu gene expression in LPS-activated CH12.LX B cells (AhR expressing) but not in BCL-1 B cells (AhR deficient). The present studies extend these previous findings by investigating the effect of TCDD on AP-1 and nuclear factor (NF)-kappaB, both of which play an important role in B-cell activation, differentiation, and immunoglobulin (Ig) gene expression. Electrophoretic mobility shift assays and chloramphenicol acetyl transferase reporter gene experiments demonstrated that lipopolysaccharide (LPS)-induced DNA binding and transcriptional activity of AP-1 was markedly inhibited by TCDD at 24, 48, and 72 h after cellular activation of CH12.LX cells. Conversely, TCDD treatment produced no significant change on the activity of NF-kappaB. Two AhR antagonists, alpha-naphthoflavone and 2,2',5,5'-tetrachlorobiphenyl, attenuated TCDD-induced inhibition of AP-1 binding in CH12.LX cells. Concordant with this result, TCDD did not inhibit LPS-induced AP-1 activity in BCL-1 B cells. Moreover, supershift analysis revealed the major component of the AP-1 complex in LPS-activated CH12.LX cells was c-Jun. Additional studies revealed that the nuclear c-jun and c-jun steady-state mRNA expression was inhibited by TCDD treatment. Collectively, these results suggest that TCDD-induced inhibition of IgM expression by B cells may be mediated, at least in part, through a down-regulation of AP-1 activity in an AhR-dependent manner.
Suh
Jaehong
J
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, Korea.
Jeon
Young Jin
YJ
Kim
Hwan Mook
HM
Kang
Jong Soon
JS
Kaminski
Norbert E
NE
Yang
Kyu-Hwan
KH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001571:Benzoflavones / Q000494:pharmacology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D017930:Genes, Reporter / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008223:Lymphoma; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001571:Benzoflavones; D004785:Environmental Pollutants; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018336:Receptors, Aryl Hydrocarbon; D018808:Transcription Factor AP-1; C009407:2,5,2',5'-tetrachlorobiphenyl; C011512:alpha-naphthoflavone; D011078:Polychlorinated Biphenyls; D015500:Chloramphenicol O-Acetyltransferase