or
Title | Aryl hydrocarbon receptor-dependent inhibition of AP-1 activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in activated B cells |
Authors | J H Suh; Y J Jeon; Hwan Mook Kim; Jong Soon Kang; N E Kaminski; Kyu-Hwan Yang |
Publisher | Elsevier |
Issue Date | 2002 |
Citation | Toxicology and Applied Pharmacology, vol. 181, no. 2, pp. 116-123 |
Keywords | AhR; AP-1; B cell; TCDD; 2,2',5,5' tetrachlorobiphenyl; 2,3,7,8 tetrachlorodibenzo para dioxin; alpha naphthoflavone; aromatic hydrocarbon receptor; biphenyl derivative; chloramphenicol acetyltransferase |
Abstract | 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)-κB, 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-κB. Two AhR antagonists, α-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. |
ISSN | 0041-008X |
Link | |
Appears in Collections | |
Registered Date |
2017-04-19 |
